Study of Lenalidomide in Combination With Sunitinib to Evaluate the Safety and Efficacy in Patients With Renal Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study was to determine the maximum tolerated dose, safety, and effectiveness of lenalidomide (CC-5013) administered in combination with sunitinib as treatment for patients with renal cell carcinoma.

Official Title
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A Phase 1/2, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of Lenalidomide in Combination With Sunitinib in Subjects With Advanced or Metastatic Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic Renal Cell Carcinoma. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. Exclusion Criteria: Prior chemotherapy. Prior treatment with lenalidomide, thalidomide, pomalidomide, or sunitinib. Laboratory values outside normal ranges. Myocardial infarction (MI) within past 12 months. Current congestive heart failure.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Participants received an oral dose of lenalidomide MTD (mg) capsule administered in combination with a single dose of sunitinib 37.5 mg on days 1-21 of each 21-day cycle | Drug: Lenalidomide<br>* Lenalidomide MTD mg by mouth (PO) daily for Days 1- 21 in combination<br>* Other names: Revlimid;Drug: Sunitinib<br>* Sunitinib 37.5 mg PO daily on days 1-21 of each 21-day cycle in Cohort A or on days 1-14 in Cohorts F and G<br>* Other names: Sutent;|
| Experimental: Cohorts F and G<br>Participants received an oral daily dose of lenalidomide on Days 1 to 21 in combination with a single oral daily dose of sunitinib 37.5 mg on days 1 to 14 or days 1 to 21 of each 21-day cycle | Drug: Lenalidomide<br>* Lenalidomide MTD mg by mouth (PO) daily for Days 1- 21 in combination<br>* Other names: Revlimid;Drug: Sunitinib<br>* Sunitinib 37.5 mg PO daily on days 1-21 of each 21-day cycle in Cohort A or on days 1-14 in Cohorts F and G<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Maximum Tolerated Dose (MTD) | The MTD of lenalidomide in combination with sunitinib was defined as the highest dose level at which no more than 1 out of 6 participants experienced a dose limiting toxicity (DLT). Dose limiting toxicities were: • Inability to deliver Lenalidomide in Cycle 1 due to a drug-related toxicity resulting in: Grade (GR) 3 or 4 non-hematological toxicity lasting for ≥ 14 days Febrile neutropenia Gr 4 neutropenia lasting for ≥ 7 days Gr 4 thrombocytopenia The occurrence of one of the above drug-related toxicities resulting in a clinical and/or laboratory assessment being done within 7 days following the initial finding to examine the participants for resolution of the toxicity. Lack of resolution of the toxicities was considered a DLT. If ≤ 7 doses of lenalidomide or Sunitinib were missed in Cycle 1 due to non-drug related event, the participant data was to be included in the evaluation of dose escalation. | Within 21 days of first dose of treatment | 
| Phase 2: Tumor Response Rate According to Response Evaluation Criteria In Solid Tumors (RECIST 1.1) | Tumor response was to be evaluated every 3 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response was to be defined by RECIST 1.1 criteria: Complete response-disappearance of all lesions Partial response-30% decrease in the sum of diameters of target lesions from baseline Stable disease-neither shrinkage nor increase of lesions. Progressive Disease-20% increase in the sum of diameters of target lesions from nadir. | After at least 3 cycles of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Lenalidomide and Sunitinib | Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participants health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death | First day of study drug to within 28 days after the last dose of the last study drug; The duration of exposure to lenalidomide and sunitinib was 7.0 to 327 and 7.0 to 328 days respectively | 
| Phase 1 : Tumor Response Rate According to RECIST 1.1 | Tumor response was evaluated every 3 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response was evaluated using the Response Criteria Evaluation in Solid Tumors (RECIST 1.1) criteria: Treatment response includes both complete response and partial response Complete response-disappearance of all lesions Partial response-30% decrease in the sum of diameters of target lesions from baseline Stable disease-neither shrinkage nor increase of lesions Progressive Disease-20% increase in the sum of diameters of target lesions from nadir | Every 3 cycles; up to month 25 | 
| Progression Free Survival (PFS) | Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. | Day 1 of study drug to disease progression or death | 
| Duration of Response | Duration of response was defined as the time from the initial response date to progressive disease (PD) for participants who achieved an objective confirmed complete response (CR) or partial response (PR) | Day 1 of initial response date to progressive disease | 
| Overall Survival (OS) | Overall survival was defined as the time from the start of study drug therapy to death. | Day 1 of study drug to death |