Trial Outcomes & Findings for Study of Panobinostat in Patients With Neuroendocrine Tumors (NCT NCT00985946)

Last Updated: 2019-12-09

Results Overview

Confirmed anti-tumor response rate will be validated by the Response Evaluation Criteria in Solid Tumors (RECIST). All participants included in the study will be assessed for response to the proposed panobinostat treatment, even if there are protocol treatment deviations. Each participant will be assigned one of the following categories: complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of other cause, or unknown.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

every 8 weeks, up to 5 years

Results posted on

2019-12-09

Participant Flow

This study actively recruited from April 2010 through May 2011 at a large cancer center in Wisconsin.

Participant milestones

Participant milestones
Measure	Panobinostat Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Overall Study STARTED	15
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Panobinostat Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Overall Study Lost to Follow-up	6
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Study of Panobinostat in Patients With Neuroendocrine Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panobinostat n=15 Participants Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Age, Customized 40-49 years of age	3 participants n=5 Participants
Age, Customized 50-59 years of age	5 participants n=5 Participants
Age, Customized 60-69 years of age	4 participants n=5 Participants
Age, Customized 70-79 years of age	2 participants n=5 Participants
Age, Customized >= 80 years of age	1 participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants

PRIMARY outcome

Timeframe: every 8 weeks, up to 5 years

Outcome measures

Outcome measures
Measure	Panobinostat n=15 Participants Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Stable Disease	15 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete Response	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Partial Response	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Progressive Disease	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Early death from malignant disease	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Early death from toxicity	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Early death because of other cause	0 participants
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Unknown	0 participants

SECONDARY outcome

Timeframe: up to 5 years

Evaluate the toxicity and tolerability of panobinostat in the patient population

Outcome measures

Outcome measures
Measure	Panobinostat n=15 Participants Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Number of Participants With Toxicities	5 participants

SECONDARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Panobinostat n=15 Participants Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat	9.9 months Interval 4.1 to 16.9

SECONDARY outcome

Timeframe: Pre-treatment and up to week 12

Population: Data to delineate the expression of Notch 1 in neuroendocrine tumor samples was not collected. The question regarding the role of Notch1 in well-differentiated NET remains unanswered.

The expression of Notch 1 in neuroendocrine tumor samples will be evaluated prior to Cycle 1 Day 1 dose and at the end of Cycle 2 of treatment of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Panobinostat n=15 Participants Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design.
Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat	47.27 months Interval 17.87 to Not reached.

Adverse Events

Panobinostat

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Panobinostat n=15 participants at risk Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual.
Metabolism and nutrition disorders Grade 3 albumin, serum low	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 1 creatinine	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Grade 3 diarrhea	13.3% 2/15 • Number of events 2 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Infections and infestations Grade 3 febrile neutropenia	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 1 glucose, serum-high (hyperglycemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Grade 2 hemoglobin	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Cardiac disorders Grade 3 hypotension	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Cardiac disorders Grade 5 hypotension (death)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Infections and infestations Grade 3 infection	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 3 lipase	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 4 lipase	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 1 magnesium, serum-low (hypomagnesemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Grade 3 pain	13.3% 2/15 • Number of events 2 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Grade 4 pain	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Hepatobiliary disorders Grade 2 pancreatitis	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Grade 4 platelets (thrombocytopenia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Grade 3 Pneumotosis Coli	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 1 potassium, serum-low (hypokalemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Grade 3 small bowel NOS	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Grade 1 sodium, serum-low (hyponatremia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.

Other adverse events

Other adverse events
Measure	Panobinostat n=15 participants at risk Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	53.3% 8/15 • Number of events 27 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Alkaline phosphatase	53.3% 8/15 • Number of events 15 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Immune system disorders Allergic rhinitis	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Immune system disorders Allergy/Immunology	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Anorexia	40.0% 6/15 • Number of events 18 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Ear and labyrinth disorders Auditory/Ear	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Injury, poisoning and procedural complications Bruising (in absence of Grade 3 or 4 thrombocytopenia)	20.0% 3/15 • Number of events 6 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	13.3% 2/15 • Number of events 4 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Musculoskeletal and connective tissue disorders Cervical spine-range of motion	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Cholesterol, serum-high (hypercholesteremia)	33.3% 5/15 • Number of events 26 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Creatinine	53.3% 8/15 • Number of events 43 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Dehydration	26.7% 4/15 • Number of events 4 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Skin and subcutaneous tissue disorders Dermatology/Skin	13.3% 2/15 • Number of events 2 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Diarrhea	86.7% 13/15 • Number of events 52 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Skin and subcutaneous tissue disorders Dry skin	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	20.0% 3/15 • Number of events 4 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Edema: limb	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Elevated Triglycerides	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Fatigue (asthenia, lethargy, malaise)	100.0% 15/15 • Number of events 68 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Flatulence	26.7% 4/15 • Number of events 9 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Vascular disorders Flushing	33.3% 5/15 • Number of events 20 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	6.7% 1/15 • Number of events 2 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Gastrointestinal	20.0% 3/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations GGT (gamma-Glutamyl transpeptidase)	53.3% 8/15 • Number of events 21 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Infections and infestations Gingivitis	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Renal and urinary disorders Glomerular filtration rate	33.3% 5/15 • Number of events 12 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	86.7% 13/15 • Number of events 61 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Heartburn/dyspepsia	13.3% 2/15 • Number of events 2 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Hemoglobin	66.7% 10/15 • Number of events 42 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Hemorrhage/Bleeding	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Vascular disorders Hypertension	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Vascular disorders Hypotension	20.0% 3/15 • Number of events 5 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Infections and infestations Infection	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations INR (International Normalized Ratio of prothrombin time)	13.3% 2/15 • Number of events 9 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Musculoskeletal and connective tissue disorders Joint-function	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Leukocytes (total WBC)	20.0% 3/15 • Number of events 18 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Lipase	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Lymphopenia	20.0% 3/15 • Number of events 8 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	26.7% 4/15 • Number of events 8 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Nervous system disorders Memory impairment	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	20.0% 3/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Skin and subcutaneous tissue disorders Nail changes	13.3% 2/15 • Number of events 3 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Nausea	86.7% 13/15 • Number of events 39 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Nervous system disorders Neuropathy: sensory	13.3% 2/15 • Number of events 8 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Nervous system disorders Neutrophils/granulocytes (ANC/AGC)	26.7% 4/15 • Number of events 16 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Pain	73.3% 11/15 • Number of events 40 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	13.3% 2/15 • Number of events 8 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Platelets	86.7% 13/15 • Number of events 73 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Potassium, serum-high (hyperkalemia)	20.0% 3/15 • Number of events 9 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Potassium, serum-low (hypokalemia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Skin and subcutaneous tissue disorders Rash/desquamation	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	33.3% 5/15 • Number of events 18 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
General disorders Sweating (diaphoresis)	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Taste alteration (dysgeusia)	26.7% 4/15 • Number of events 5 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Vascular disorders Thrombosis/thrombus/embolism	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Blood and lymphatic system disorders Thrombotic microangiopathy	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Endocrine disorders Thyroid function, high (hyperthyroidism, thyrotoxicosis)	26.7% 4/15 • Number of events 6 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Endocrine disorders Thyroid function, low (hypothyroidism)	53.3% 8/15 • Number of events 26 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Ear and labyrinth disorders Tinnitus	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Nervous system disorders Tremor	6.7% 1/15 • Number of events 4 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Metabolism and nutrition disorders Triglyceride, serum-high (hypertriglyceridemia)	53.3% 8/15 • Number of events 51 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Renal and urinary disorders Urinary frequency/urgency	6.7% 1/15 • Number of events 1 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Gastrointestinal disorders Vomiting	53.3% 8/15 • Number of events 17 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
Investigations Weight loss	60.0% 9/15 • Number of events 37 • Adverse events were collected for 5 years. Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE. Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.

Additional Information

Noelle LoConte

University of Wisconsin Carbone Cancer Center

Phone: 608-265-5883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place