A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether lenalidomide in combination with cetuximab is safe and effective in patients with KRAS mutant colorectal cancer.

Official Title
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A Phase 2, Open-Label Study To Evaluate The Efficacy And Safety Of Lenalidomide In Combination With Cetuximab In Pretreated Subjects With K-Ras Mutant Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: cetuximab
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic colorectal adenocarcinoma. Confirmed K-RAS mutant tumor Disease progression on oxaliplatin- AND irinotecan-containing regimens, with at least one of these regimens containing bevacizumab. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. Exclusion Criteria: Use of chemotherapy, hormonal therapy, immunotherapy or any other cancer or experimental treatment ≤ 28 days prior to the first day of the first cycle. Radiotherapy for up to ≥ 30% of the bone marrow. Surgery ≤ 28 days before day 1 of the first cycle (minimally invasive interventions for diagnostic purposes or disease staging are permitted). Previous treatment with cetuximab, panitumumab, pomalidomide (CC-4047), lenalidomide or thalidomide. Untreated, symptomatic brain metastases (brain imaging not required). Venous thromboembolism ≤ 6 months before day1 of the first cycle. Current congestive heart failure (classes II to IV of the New York Heart Association). Myocardial infarction ≤ 12 months before day1 of the first cycle. Uncontrolled hypertension.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lenalidomide plus cetuximab<br>Combination therapy of lenalidomide plus cetuximab | Drug: cetuximab<br>* Intravenous infusions of cetuximab (400 mg/m^2 Cycle 1 Day 1, thereafter 250 mg/m^2), administered on days 1, 8, 15 and 22 of each 28 day cycle.<br>* Other names: Erbitux;Drug: lenalidomide<br>* Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle<br>* Other names: Revlimid;|
| Experimental: lenalidomide<br>Single agent therapy of lenalidomide | Drug: lenalidomide<br>* Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period | The number of participants with DLTs determines the maximum tolerated dose of the combination therapy used in the Proof of Concept (POC) period: If <2 of the initial 6 participants experience a DLT, then the POC will start with lenalidomide at 25 mg. If ≥2 of the initial 6 participants experienced a DLT, then 6 more subjects were to be enrolled at 20 mg lenalidomide. If <2 of the additional 6 subjects experienced a DLT, then the lenalidomide starting dose for the POC was to be 20 mg. If ≥2 of the additional 6 subjects experienced a DLT, then 6 more subjects were to be enrolled at 15 mg lenalidomide. If <2 of the additional 6 subjects experienced a DLT, then the POC was to start with lenalidomide at 15 mg. If ≥2 of the additional 6 subjects experienced a DLT, the dosing for the study was to be reassessed by Celgene Corporation and the investigators. | Up to Day 28 (Cycle 1) | 
| Percentage of Participants With a Response to Treatment During the Proof of Concept Period | Tumor response was evaluated every 2 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response and progression were evaluated using the RECIST 1.1 criteria (Eisenhauer, 2009). 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 Analysis was not performed due to the early termination of the study. | week 9 up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimates for Progression Free Survival (PFS) | PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD), or death on study due to any cause. Analysis was not performed due to the early termination of the study. | up to week 24 | 
| Kaplan-Meier Estimates for 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). Analysis was not performed due to the early termination of the study. | up to week 24 | 
| Percentage of Participants With Disease Control | Known as the Disease Control Rate (DCR), participants with a complete response, partial response or stable disease contribute to the DCR. This analysis was not performed due to the early termination of the study. | up to week 24 | 
| Kaplan-Meier Estimates for Overall Survival | Overall survival was defined as the time between randomization and death. It was intended that participants would be followed for up to 5 years following discontinuation from treatment. Analysis was not performed due to the early termination of the study. | up to 5.5 years | 
| Participants With Treatment-Emergent Adverse Events (TEAE) | TEAEs are any adverse event occurring or worsening on or after the first treatment of any study drug and within 28 days after the last dose of the last study drug received. Relation to study drug was determined by the investigator. Severity of AE is graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.0. Severity is a 5-point scale: 3= severe or medically significant but not life-threatening 4=life-threatening, urgent intervention required 5=death related to AE. | up to week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Revlimid, Lenalidomide, Cetuximab, Erbitux, KRAS