Trial Outcomes & Findings for S0904: Docetaxel With or Without Vandetanib in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer (NCT NCT00872989)

Last Updated: 2016-12-19

Results Overview

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years

Results posted on

2016-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I: Docetaxel Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally
Overall Study STARTED	66	63
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	65	63

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I: Docetaxel Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally
Overall Study Adverse Event	7	15
Overall Study Withdrawal by Subject	8	5
Overall Study Progression/relapse	47	35
Overall Study Not protocol specified	3	8

Baseline Characteristics

S0904: Docetaxel With or Without Vandetanib in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Docetaxel n=66 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib n=63 Participants Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Total n=129 Participants Total of all reporting groups
Age, Continuous	61.7 years n=5 Participants	61.9 years n=7 Participants	61.9 years n=5 Participants
Gender Female	66 Participants n=5 Participants	63 Participants n=7 Participants	129 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	58 participants n=5 Participants	56 participants n=7 Participants	114 participants n=5 Participants
Race/Ethnicity, Customized Black	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Hispanic Yes	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Hispanic No	64 participants n=5 Participants	58 participants n=7 Participants	122 participants n=5 Participants
Hispanic Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Prior Antiangiogenic Therapy Yes	12 participants n=5 Participants	9 participants n=7 Participants	21 participants n=5 Participants
Prior Antiangiogenic Therapy No	54 participants n=5 Participants	54 participants n=7 Participants	108 participants n=5 Participants
Primary Site Fallopian Tube	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Primary Site Ovary	56 participants n=5 Participants	53 participants n=7 Participants	109 participants n=5 Participants
Primary Site Peritoneal	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Performance Status 0	37 participants n=5 Participants	33 participants n=7 Participants	70 participants n=5 Participants
Performance Status 1	27 participants n=5 Participants	26 participants n=7 Participants	53 participants n=5 Participants
Performance Status 2	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Baseline serum level of cancer-antigen 125 (CA-125) ≤ 35 units/mL	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
Baseline serum level of cancer-antigen 125 (CA-125) > 35 units/mL	49 participants n=5 Participants	53 participants n=7 Participants	102 participants n=5 Participants
Prior treatment with platinum for recurrent disease	34 participants n=5 Participants	28 participants n=7 Participants	62 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=66 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib n=63 Participants Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib
Progression Free Survival (PFS)	3.5 months Interval 2.3 to 4.6	3.0 months Interval 1.6 to 4.3	—

SECONDARY outcome

Timeframe: Disease assessment for responses were performed every 6 weeks for as long as the patient remained on protocol treatment, up to 5 years.

Population: Analysis of response is in the subset of patients who had at least one measurable target lesion at baseline.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR in conjunction with measured CA125 responses

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=57 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib n=52 Participants Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Complete Response	0 participants	0 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Partial Response	5 participants	6 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Unconfirmed Complete Response	1 participants	0 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Unconfirmed Partial Response	2 participants	2 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Stable/No Response	19 participants	17 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Increasing Disease	23 participants	20 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Symptomatic Deterioration	0 participants	1 participants	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease Assessment Inadequate	7 participants	6 participants	—

SECONDARY outcome

Timeframe: every 3 months for two years and then every 6 months for 3 years

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=66 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib n=63 Participants Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib
Overall Survival	18 months Interval 13.7 to 26.1	14 months Interval 9.9 to 19.7	—

SECONDARY outcome

Timeframe: Toxicity assessment was evaluated before each treatment cycle (21 days), up to 5 years.

Population: Eligible patients who had received the protocol treatments were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=64 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib n=61 Participants Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib n=33 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Abdominal pain	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Allergic reaction	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anemia	1 Participants	2 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anorexia	1 Participants	2 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Ascites	0 Participants	0 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Bladder infection	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Chest pain - cardiac	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Constipation	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dehydration	3 Participants	3 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Depression	0 Participants	0 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	2 Participants	5 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	0 Participants	2 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Edema limbs	1 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	6 Participants	5 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Febrile neutropenia	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Gastrointestinal pain	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Generalized muscle weakness	1 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypercalcemia	1 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyperglycemia	1 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypertension	0 Participants	0 Participants	2 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypocalcemia	2 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypokalemia	1 Participants	1 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypomagnesemia	1 Participants	2 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyponatremia	1 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypotension	1 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Leukocytosis	1 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	2 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Mucositis oral	1 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Myalgia	0 Participants	0 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nail infection	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	5 Participants	2 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	32 Participants	28 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Palmar-plantar erythrodysesthesia syndrome	1 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Papulopustular rash	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Peripheral sensory neuropathy	3 Participants	0 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pneumonitis	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pruritus	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash acneiform	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash maculo-papular	0 Participants	4 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Sinus bradycardia	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Skin and subcutaneous tissue disorders - Other	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Stoma site infection	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Thromboembolic event	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Treatment related secondary malignancy	0 Participants	1 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Urinary tract infection	0 Participants	2 Participants	0 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	3 Participants	3 Participants	1 Participants
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	20 Participants	20 Participants	0 Participants

SECONDARY outcome

Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.

Time to treatment failure after treatment with single agent vandetanib following progression on single agent docetaxel. Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=33 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib
Time to Treatment Failure	1.4 Months Interval 1.3 to 1.6	—	—

SECONDARY outcome

Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.

Population: Analysis of response is in the subset of patients who had at least one measurable target lesion at baseline.

Outcome measures

Outcome measures
Measure	Arm I: Docetaxel n=30 Participants Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Arm II: Docetaxel + Vandetanib Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV vandetanib: Given orally	Vandetanib
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Complete Response	0 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Partial Response	0 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Unconfirmed Complete Response	0 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Unconfirmed Partial Response	1 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Stable/No Response	8 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Increasing Disease	20 participants	—	—
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel Assessment Inadequate	1 participants	—	—

Adverse Events

Docetaxel

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Docetaxel + Vandetanib

Serious events: 31 serious events

Other events: 59 other events

Deaths: 0 deaths

Vandetanib

Serious events: 7 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Lung Committee Statistician

SWOG Statisticial Center

Phone: 206-667-4623

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Docetaxel n=64 participants at risk Adverse events are analyzed in the subset of patients who received at least one dose of drug.	Docetaxel + Vandetanib n=61 participants at risk Adverse events are analyzed in the subset of patients who received at least one dose of drug.	Vandetanib n=33 participants at risk Adverse events are analyzed in the subset of patients who received at least one dose of drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Vascular disorders Hypertension	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Blood and lymphatic system disorders Anemia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Cardiac disorders Chest pain - cardiac	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Cardiac disorders Pericardial effusion	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Cardiac disorders Sinus bradycardia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Abdominal distension	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Abdominal pain	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Ascites	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	9.1% 3/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Colonic obstruction	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Constipation	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Diarrhea	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Mucositis oral	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Nausea	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	6.1% 2/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Obstruction gastric	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Gastrointestinal disorders Vomiting	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	6.1% 2/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
General disorders Death NOS	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
General disorders Fatigue	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
General disorders General disorders and admin site conditions - Other	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
General disorders Pain	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Infections and infestations Bronchial infection	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Infections and infestations Device related infection	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Infections and infestations Sepsis	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Infections and infestations Skin infection	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Infections and infestations Urinary tract infection	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Injury, poisoning and procedural complications Wound complication	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Investigations Lymphocyte count decreased	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Investigations Neutrophil count decreased	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	31.1% 19/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Investigations White blood cell decreased	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	6.6% 4/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Anorexia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	9.1% 3/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Dehydration	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	6.6% 4/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	6.1% 2/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	4.9% 3/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.3% 2/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	3.0% 1/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Metabolism and nutrition disorders Hypomagnesemia	1.6% 1/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/64 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	1.6% 1/61 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.	0.00% 0/33 • Toxicity assessments was evaluated before each treatment cycle (21 days), up to 5 years.