Trial Outcomes & Findings for Sunitinib Malate as Maintenance Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy (NCT NCT00693992)

Last Updated: 2019-06-11

Results Overview

Progression Free Survival (PFS) was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

210 participants

Primary outcome timeframe

Time from randomization to disease progression and death of any cause, whichever comes first (up to 5 years)

Results posted on

2019-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Sunitinib Malate) Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Overall Study STARTED	106	104
Overall Study COMPLETED	106	104
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sunitinib Malate as Maintenance Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Sunitinib Malate) n=106 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=104 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies	Total n=210 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	67 years n=7 Participants	66 years n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	44 Participants n=7 Participants	93 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	60 Participants n=7 Participants	117 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	87 Participants n=5 Participants	85 Participants n=7 Participants	172 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	106 participants n=5 Participants	104 participants n=7 Participants	210 participants n=5 Participants

PRIMARY outcome

Timeframe: Time from randomization to disease progression and death of any cause, whichever comes first (up to 5 years)

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=106 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=104 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Progression Free Survival (PFS)	4.3 months Interval 3.2 to 4.9	2.6 months Interval 1.8 to 3.0

SECONDARY outcome

Timeframe: Time from randomization to death (up to 5 years)

Overall survival (OS) is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=106 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=104 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Overall Survival (OS)	11.7 months Interval 9.9 to 14.0	12.1 months Interval 9.8 to 15.3

SECONDARY outcome

Timeframe: Duration of treatment (up to 5 years)

The percentage of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=106 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=104 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Response Rate (RR)	11 percentage of participants	5 percentage of participants

SECONDARY outcome

Timeframe: At 3 months

Population: Patients who completed the EORTC-QLQ-C30 Global Health Subscale at baseline and 3 months were included in this analysis.

The percentage of patients with at least a 10% drop in the EORTC-QLQ-C30 Global Health Subscale score from baseline to 3-months. The difference between groups will be tested using Fisher's exact test.

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=80 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=83 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Percentage of Deterioration in QOL at 3 Months Using the EORTC QLQ-C30 Global Health Subscale	55.8 percentage of patients	28.6 percentage of patients

SECONDARY outcome

Timeframe: At 3 months

Population: Patients who completed the EORTC LC13 Dyspnea Subscale at baseline and 3 months were included in this analysis.

The percentage of patients with at least a 10% drop in the EORTC LC13 Dyspnea Subscale score from baseline to 3-months. The difference between groups will be tested using Fisher's exact test.

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=83 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=85 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Percentage of Deterioration in Symptom Progression at 3 Months Using the EORTC LC13 Dyspnea Subscale	31.5 percentage of patients	29.3 percentage of patients

SECONDARY outcome

Timeframe: Duration of study (up to 5 years)

Population: 189 participants were evaluable for adverse events.

Grade 3 or 4 adverse events which affected more than 5% of participants are summarized by arm.

Outcome measures

Outcome measures
Measure	Arm I (Sunitinib Malate) n=97 Participants Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=92 Participants Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Anemia	6 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Fatigue	26 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Thrombocytopenia	12 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Hypertension	12 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Rash	11 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Mucositis	11 percentage of participants	0 percentage of participants
Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Neutropenia	7 percentage of participants	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 weeks

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Sunitinib Malate)

Serious events: 33 serious events

Other events: 87 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 14 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mark A. Socinski, M.D.

University of Pittsburgh

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Sunitinib Malate) n=97 participants at risk Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=92 participants at risk Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Blood and lymphatic system disorders Hemoglobin decreased	10.3% 10/97 • Number of events 11 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Blood and lymphatic system disorders Hemolysis	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Cardiac disorders Cardiac disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Cardiac disorders Conduction disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Cardiac disorders Left ventricular failure	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Cardiac disorders Myocardial ischemia	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Cardiac disorders Palpitations	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Ear and labyrinth disorders External ear inflammation	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Endocrine disorders Hypothyroidism	2.1% 2/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Constipation	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	5.2% 5/97 • Number of events 6 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Gastrointestinal disorders Duodenal hemorrhage	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Dysphagia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Mucositis oral	5.2% 5/97 • Number of events 5 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Nausea	9.3% 9/97 • Number of events 10 189 participants were evaluable for adverse events.	5.4% 5/92 • Number of events 5 189 participants were evaluable for adverse events.
Gastrointestinal disorders Oral hemorrhage	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Pancreatitis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Vomiting	4.1% 4/97 • Number of events 4 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
General disorders Chest pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Fatigue	26.8% 26/97 • Number of events 34 189 participants were evaluable for adverse events.	8.7% 8/92 • Number of events 9 189 participants were evaluable for adverse events.
General disorders Fever	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Localized edema	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Pain	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Sudden death	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Hepatobiliary disorders Cholecystitis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Immune system disorders Immune system disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Infections and infestations Infection without neutropenia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Infections and infestations Pneumonia	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Infections and infestations Sepsis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Infections and infestations Skin infection	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Infections and infestations Urinary tract infection	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Fracture	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Alanine aminotransferase increased	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Alkaline phosphatase increased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Amylase increased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	4.1% 4/97 • Number of events 4 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Electrocardiogram QTc interval prolonged	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Leukocyte count decreased	3.1% 3/97 • Number of events 4 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Investigations Lipase increased	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Lymphocyte count decreased	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Neutrophil count decreased	4.1% 4/97 • Number of events 4 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Platelet count decreased	9.3% 9/97 • Number of events 11 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	12.4% 12/97 • Number of events 13 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 3 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Blood glucose increased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Dehydration	4.1% 4/97 • Number of events 4 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum albumin decreased	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum calcium decreased	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum magnesium decreased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum phosphate decreased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum potassium increased	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium decreased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium increased	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Neck pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Cognitive disturbance	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Depressed level of consciousness	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Dizziness	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Dysgeusia	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Encephalopathy	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Headache	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Ischemia cerebrovascular	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Peripheral motor neuropathy	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Syncope	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Psychiatric disorders Confusion	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Psychiatric disorders Depression	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Psychiatric disorders Insomnia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Renal and urinary disorders Proteinuria	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Renal and urinary disorders Renal failure	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.2% 7/97 • Number of events 7 189 participants were evaluable for adverse events.	5.4% 5/92 • Number of events 5 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	6.2% 6/97 • Number of events 8 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hypopigmentation	2.1% 2/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Vascular disorders Hypertension	7.2% 7/97 • Number of events 8 189 participants were evaluable for adverse events.	3.3% 3/92 • Number of events 3 189 participants were evaluable for adverse events.
Vascular disorders Thrombosis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 2 189 participants were evaluable for adverse events.

Measure	Arm I (Sunitinib Malate) n=97 participants at risk Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Sunitinib Malate: Given PO	Arm II (Placebo) n=92 participants at risk Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO Quality-of-Life Assessment: Ancillary studies
Blood and lymphatic system disorders Hemoglobin decreased	9.3% 9/97 • Number of events 28 189 participants were evaluable for adverse events.	3.3% 3/92 • Number of events 6 189 participants were evaluable for adverse events.
Blood and lymphatic system disorders Hemolysis	0.00% 0/97 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 9 189 participants were evaluable for adverse events.
Cardiac disorders Left ventricular failure	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 4 189 participants were evaluable for adverse events.
Cardiac disorders Sinus bradycardia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Cardiac disorders Ventricular tachycardia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Ear and labyrinth disorders External ear inflammation	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Endocrine disorders Hypothyroidism	5.2% 5/97 • Number of events 11 189 participants were evaluable for adverse events.	5.4% 5/92 • Number of events 7 189 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 3 189 participants were evaluable for adverse events.
Gastrointestinal disorders Constipation	0.00% 0/97 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 3 189 participants were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	45.4% 44/97 • Number of events 112 189 participants were evaluable for adverse events.	16.3% 15/92 • Number of events 37 189 participants were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Dysphagia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Flatulence	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Gastritis	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Mouth necrosis	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Mucositis oral	35.1% 34/97 • Number of events 71 189 participants were evaluable for adverse events.	7.6% 7/92 • Number of events 14 189 participants were evaluable for adverse events.
Gastrointestinal disorders Nausea	38.1% 37/97 • Number of events 73 189 participants were evaluable for adverse events.	21.7% 20/92 • Number of events 42 189 participants were evaluable for adverse events.
Gastrointestinal disorders Stomach pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Gastrointestinal disorders Vomiting	5.2% 5/97 • Number of events 10 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
General disorders Chest pain	3.1% 3/97 • Number of events 4 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Edema limbs	0.00% 0/97 189 participants were evaluable for adverse events.	4.3% 4/92 • Number of events 13 189 participants were evaluable for adverse events.
General disorders Fatigue	71.1% 69/97 • Number of events 218 189 participants were evaluable for adverse events.	72.8% 67/92 • Number of events 204 189 participants were evaluable for adverse events.
General disorders Fever	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Localized edema	1.0% 1/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
General disorders Pain	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Immune system disorders Immune system disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Infections and infestations Pneumonia	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Bruising	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Fracture	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Injury to superior vena cava	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Investigations Alanine aminotransferase increased	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Investigations Alkaline phosphatase increased	2.1% 2/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Amylase increased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 4 189 participants were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Investigations CD4 lymphocytes decreased	2.1% 2/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Creatinine increased	1.0% 1/97 • Number of events 12 189 participants were evaluable for adverse events.	3.3% 3/92 • Number of events 15 189 participants were evaluable for adverse events.
Investigations Electrocardiogram QTc interval prolonged	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 4 189 participants were evaluable for adverse events.
Investigations Leukocyte count decreased	7.2% 7/97 • Number of events 23 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 9 189 participants were evaluable for adverse events.
Investigations Lipase increased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 4 189 participants were evaluable for adverse events.
Investigations Lymphocyte count decreased	3.1% 3/97 • Number of events 6 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Investigations Neutrophil count decreased	10.3% 10/97 • Number of events 23 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Investigations Platelet count decreased	13.4% 13/97 • Number of events 24 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 2 189 participants were evaluable for adverse events.
Investigations Weight loss	4.1% 4/97 • Number of events 6 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	33.0% 32/97 • Number of events 83 189 participants were evaluable for adverse events.	20.7% 19/92 • Number of events 34 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Blood glucose increased	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	7.6% 7/92 • Number of events 31 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Blood uric acid increased	1.0% 1/97 • Number of events 12 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum albumin decreased	3.1% 3/97 • Number of events 7 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum calcium increased	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 3 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum glucose decreased	0.00% 0/97 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum magnesium decreased	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 7 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum phosphate decreased	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 6 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum potassium decreased	2.1% 2/97 • Number of events 3 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 7 189 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium decreased	4.1% 4/97 • Number of events 8 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 3 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	3.1% 3/97 • Number of events 5 189 participants were evaluable for adverse events.	6.5% 6/92 • Number of events 12 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	1.0% 1/97 • Number of events 3 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	1.0% 1/97 • Number of events 3 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 3 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Neck pain	1.0% 1/97 • Number of events 4 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 3/97 • Number of events 3 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Nervous system disorders Accessory nerve disorder	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Depressed level of consciousness	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Dizziness	0.00% 0/97 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Nervous system disorders Dysgeusia	4.1% 4/97 • Number of events 8 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Nervous system disorders Headache	15.5% 15/97 • Number of events 27 189 participants were evaluable for adverse events.	13.0% 12/92 • Number of events 26 189 participants were evaluable for adverse events.
Nervous system disorders Ischemia cerebrovascular	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Nervous system disorders Peripheral motor neuropathy	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 2 189 participants were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	6.2% 6/97 • Number of events 15 189 participants were evaluable for adverse events.	5.4% 5/92 • Number of events 7 189 participants were evaluable for adverse events.
Nervous system disorders Syncope	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Psychiatric disorders Agitation	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 6 189 participants were evaluable for adverse events.
Psychiatric disorders Anxiety	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Psychiatric disorders Confusion	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Psychiatric disorders Depression	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.
Psychiatric disorders Insomnia	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Renal and urinary disorders Renal failure	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 5/97 • Number of events 7 189 participants were evaluable for adverse events.	5.4% 5/92 • Number of events 13 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.2% 5/97 • Number of events 7 189 participants were evaluable for adverse events.	6.5% 6/92 • Number of events 23 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.1% 4/97 • Number of events 6 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Mediastinal hemorrhage	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	1.0% 1/97 • Number of events 2 189 participants were evaluable for adverse events.	2.2% 2/92 • Number of events 2 189 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory tract hemorrhage	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 3 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Alopecia	1.0% 1/97 • Number of events 1 189 participants were evaluable for adverse events.	3.3% 3/92 • Number of events 4 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	28.9% 28/97 • Number of events 83 189 participants were evaluable for adverse events.	8.7% 8/92 • Number of events 14 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash desquamating	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 2 189 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hypopigmentation	9.3% 9/97 • Number of events 21 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Vascular disorders Hemorrhage	2.1% 2/97 • Number of events 2 189 participants were evaluable for adverse events.	0.00% 0/92 189 participants were evaluable for adverse events.
Vascular disorders Hypertension	29.9% 29/97 • Number of events 81 189 participants were evaluable for adverse events.	14.1% 13/92 • Number of events 41 189 participants were evaluable for adverse events.
Vascular disorders Thrombosis	0.00% 0/97 189 participants were evaluable for adverse events.	1.1% 1/92 • Number of events 1 189 participants were evaluable for adverse events.