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

Experimentell: 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

Läkemedel: Lenalidomide

Lenalidomide MTD mg by mouth (PO) daily for Days 1- 21 in combination

Andra namn:

• CC-5013
• Revlimid

Läkemedel: Sunitinib

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

Andra namn:

• Sutent

Experimentell: 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

Läkemedel: Lenalidomide

Lenalidomide MTD mg by mouth (PO) daily for Days 1- 21 in combination

Andra namn:

• CC-5013
• Revlimid

Läkemedel: Sunitinib

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

Andra namn:

• Sutent

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.

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.

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

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

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.

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)

Overall Survival (OS)

Overall survival was defined as the time from the start of study drug therapy to death.