Trial Outcomes & Findings for Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma (NCT NCT00474929)

Last Updated: 2019-08-20

Results Overview

The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). Dose-limiting toxicity (DLT) is defined as an adverse event attributed (definitely, probably, or possibly) in first cycle to the study treatment and meeting the following criteria: * Grade 4 infection * Grade 4 ANC or PLT * Grade 3 or higher non-hematologic adverse event. NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 will be used to assess adverse events. For this endpoint, the number of patients reporting a DLT event are tabulated.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

103 participants

Primary outcome timeframe

First cycle (28 days) of study treatment

Results posted on

2019-08-20

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I, Dose Level 0 Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 Phase I: Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 Phase I: Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 Phase I: Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day	Phase II Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;
Overall Study STARTED	6	6	7	7	77
Overall Study COMPLETED	6	5	5	5	77
Overall Study NOT COMPLETED	0	1	2	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I, Dose Level 1 Phase I: Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 Phase I: Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 Phase I: Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day
Overall Study Withdrawal by Subject	1	0	0
Overall Study Unrelated medical condition	0	1	0
Overall Study Physician Decision	0	1	2

Baseline Characteristics

Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I, Dose Level 0 n=6 Participants Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day;	Phase I, Dose Level 1 n=5 Participants Phase I: Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 n=5 Participants Phase I: Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 n=5 Participants Phase I: Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day	Phase II n=77 Participants Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;	Total n=98 Participants Total of all reporting groups
Age, Continuous	43 years n=5 Participants	63 years n=7 Participants	56 years n=5 Participants	61 years n=4 Participants	61 years n=21 Participants	61 years n=8 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	30 Participants n=21 Participants	36 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	47 Participants n=21 Participants	62 Participants n=8 Participants
Region of Enrollment United States	6 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	77 participants n=21 Participants	98 participants n=8 Participants

PRIMARY outcome

Timeframe: First cycle (28 days) of study treatment

Outcome measures

Outcome measures
Measure	Phase I, Dose Level 0 n=6 Participants Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 n=5 Participants Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 n=5 Participants Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 n=5 Participants Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day
Number of Participants Reporting a Dose Limiting Toxicity (DLT)	1 participants	0 participants	1 participants	2 participants

PRIMARY outcome

Timeframe: Up to 12 cycles of treatment

A confirmed response is defined to be a CR or PR noted as the objective status for eligible patients during cycles 1-12. Complete Response (CR): * Multiple Myeloma (MM): Negative immunofixation of serum and urine, disappearance of soft tissue plasmacytomas, and normalization of free light chain (FLC) ratio. * Lymphoma: Disappearance of all clinical and radiographic evidence of disease, all lymph nodes of normal size (1.5 cm or less), no splenomegaly. Partial Response (PR): * MM: 50% reduction of serum or urine M-protein or to less than 200mg/day, a 50% reduction in the difference between involved and uninvolved FLC, and 50% reduction in the size of soft tissue plasmacytoma. * Lymphoma: 50% or greater reduction in sum of the products of the dimension for nodal masses; no increase in liver, spleen or node size; no new sites of disease; and a 50% decrease in lymphocyte count if followed at baseline.

Outcome measures

Outcome measures
Measure	Phase I, Dose Level 0 n=82 Participants Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day
Proportion of Confirmed Tumor Responses Complete Response (CR)	8.5 percentage of participants	—	—	—
Proportion of Confirmed Tumor Responses Partial Response (PR)	15.9 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years from registration

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Phase I, Dose Level 0 n=82 Participants Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day
Survival Time	13.5 months Interval 10.3 to 21.1	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years from registration

Progression Free Survival is defined as the time from registration to the earliest date documentation of disease progression or death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Phase I, Dose Level 0 n=82 Participants Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day
Progression Free Survival	4.6 months Interval 3.6 to 6.2	—	—	—

Adverse Events

Phase I, Dose Level 0

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I, Dose Level 1

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Phase I, Dose Level 2

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Phase I, Dose Level 3

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Phase II

Serious events: 22 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I, Dose Level 0 n=6 participants at risk Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 n=5 participants at risk Phase I: Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 n=5 participants at risk Phase I: Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 n=5 participants at risk Phase I: Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day	Phase II n=77 participants at risk Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;
Gastrointestinal disorders Diarrhea	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Ear, nose and throat examination abnormal	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Blood and lymphatic system disorders Hemoglobin decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	3.9% 3/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Cardiac disorders Cardiac valve disease	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Cardiac disorders Sinus bradycardia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Nausea	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Death	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Disease progression	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Fatigue	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Fever	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Sudden death	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Immune system disorders Hypersensitivity	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Infectious colitis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Sepsis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Bilirubin increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Leukocyte count decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Lymphocyte count decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Platelet count decreased	16.7% 1/6 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Ataxia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Rash desquamating	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Vascular disorders Hypotension	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Vascular disorders Thrombosis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.

Other adverse events

Other adverse events
Measure	Phase I, Dose Level 0 n=6 participants at risk Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day	Phase I, Dose Level 1 n=5 participants at risk Phase I: Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 2 n=5 participants at risk Phase I: Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day	Phase I, Dose Level 3 n=5 participants at risk Phase I: Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day	Phase II n=77 participants at risk Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Gingival infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Blood and lymphatic system disorders Hemoglobin decreased	50.0% 3/6 • Number of events 13 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 12 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 15 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.3% 31/77 • Number of events 63 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Blood and lymphatic system disorders Hemolysis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Blood and lymphatic system disorders Thrombotic microangiopathy	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Cardiac disorders Atrial fibrillation	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Cardiac disorders Cardiac disorder	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Ear and labyrinth disorders Hearing loss	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Endocrine disorders Adrenal insufficiency	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Endocrine disorders Hyperthyroidism	16.7% 1/6 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Constipation	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Diarrhea	50.0% 3/6 • Number of events 12 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 10 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	100.0% 5/5 • Number of events 20 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	68.8% 53/77 • Number of events 266 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Dry mouth	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Ear, nose and throat examination abnormal	16.7% 1/6 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.8% 16/77 • Number of events 35 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Enteritis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Gingival pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Hemorrhoids	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Nausea	83.3% 5/6 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	45.5% 35/77 • Number of events 90 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Oral pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Stomach pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Toothache	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Gastrointestinal disorders Vomiting	50.0% 3/6 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	26.0% 20/77 • Number of events 27 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Chills	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Death	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Edema limbs	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	3.9% 3/77 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Fatigue	100.0% 6/6 • Number of events 33 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 19 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	80.0% 4/5 • Number of events 26 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	87.0% 67/77 • Number of events 357 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
General disorders Fever	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Immune system disorders Hypersensitivity	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Bronchitis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Kidney infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Otitis externa	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Pneumonia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Sepsis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Sinusitis	16.7% 1/6 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Skin infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Soft tissue infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Tooth infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Upper respiratory infection	16.7% 1/6 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Infections and infestations Urinary tract infection	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Injury, poisoning and procedural complications Intraoperative respiratory injury - Nasal cavity	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Alanine aminotransferase increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Alkaline phosphatase increased	16.7% 1/6 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 12 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	3.9% 3/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Bilirubin increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Creatine phosphokinase increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Creatinine increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Laboratory test abnormal	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Leukocyte count decreased	33.3% 2/6 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	100.0% 5/5 • Number of events 18 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	29.9% 23/77 • Number of events 50 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Lymphocyte count decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	7.8% 6/77 • Number of events 23 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Neutrophil count decreased	33.3% 2/6 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	100.0% 5/5 • Number of events 20 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	24.7% 19/77 • Number of events 34 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Platelet count decreased	50.0% 3/6 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 22 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	41.6% 32/77 • Number of events 99 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Serum cholesterol increased	16.7% 1/6 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Investigations Weight loss	16.7% 1/6 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	7.8% 6/77 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Blood glucose increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	5.2% 4/77 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Serum calcium decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Serum phosphate decreased	33.3% 2/6 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	13.0% 10/77 • Number of events 27 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Serum potassium decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Serum sodium decreased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Metabolism and nutrition disorders Serum triglycerides increased	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	6.5% 5/77 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Joint pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Dizziness	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Headache	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Ischemia cerebrovascular	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Nervous system disorders Taste alteration	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Psychiatric disorders Depression	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Psychiatric disorders Insomnia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Renal and urinary disorders Bladder obstruction	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Renal and urinary disorders Ureteric obstruction	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	3.9% 3/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Hemorrhage nasal	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	3.9% 3/77 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/77 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	16.7% 1/6 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	40.0% 2/5 • Number of events 13 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.8% 16/77 • Number of events 78 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Rash desquamating	66.7% 4/6 • Number of events 10 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	60.0% 3/5 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	100.0% 5/5 • Number of events 8 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	54.5% 42/77 • Number of events 105 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Scalp pain	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	2.6% 2/77 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Vascular disorders Hypertension	16.7% 1/6 • Number of events 7 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 3 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 4 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	23.4% 18/77 • Number of events 76 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.
Vascular disorders Thrombosis	0.00% 0/6 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	20.0% 1/5 • Number of events 2 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	0.00% 0/5 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.	1.3% 1/77 • Number of events 1 • The adverse events reported here occurred during treatment. The maximum treatment length was 27, 28-day cycles. Adverse events were collected at the end of each cycle.

Additional Information

Thomas E. Witzig, M.D.

Mayo Clinic

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place