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
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- Renal Cell Carcinoma
- Sponsor
- Celgene
- Enrollment
- 16
- Locations
- 3
- Primary Endpoint
- Phase 1: Maximum Tolerated Dose (MTD)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Cohort A
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
Intervention: Lenalidomide
Cohort A
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
Intervention: Sunitinib
Cohorts F and G
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
Intervention: Lenalidomide
Cohorts F and G
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
Intervention: Sunitinib
Outcomes
Primary Outcomes
Phase 1: Maximum Tolerated Dose (MTD)
Time Frame: Within 21 days of first dose of treatment
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.
Phase 2: Tumor Response Rate According to Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Time Frame: After at least 3 cycles of treatment
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.
Secondary Outcomes
- Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Lenalidomide and Sunitinib(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(Every 3 cycles; up to month 25)
- Progression Free Survival (PFS)(Day 1 of study drug to disease progression or death)
- Duration of Response(Day 1 of initial response date to progressive disease)
- Overall Survival (OS)(Day 1 of study drug to death)