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

Phase 2

Terminated

• Conditions: Colorectal Cancer
• Interventions: Drug: cetuximab; Drug: lenalidomide

• Registration Number: NCT01032291
• Lead Sponsor: Celgene Corporation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2009-12-14
• Study First Submitted QC: 2009-12-14
• Study First Posted: 2009-12-15
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Status Verified: 2013-04
• Results First Submitted: 2013-04-01
• Results First Submitted QC: 2013-04-01
• Last Update Submitted: 2013-04-01
• Results First Posted: 2013-05-21
• Last Update Posted: 2013-05-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

1. Metastatic colorectal adenocarcinoma.
2. Confirmed K-RAS mutant tumor
3. Disease progression on oxaliplatin- AND irinotecan-containing regimens, with at least one of these regimens containing bevacizumab.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

Exclusion Criteria

1. Use of chemotherapy, hormonal therapy, immunotherapy or any other cancer or experimental treatment ≤ 28 days prior to the first day of the first cycle.
2. Radiotherapy for up to ≥ 30% of the bone marrow.
3. Surgery ≤ 28 days before day 1 of the first cycle (minimally invasive interventions for diagnostic purposes or disease staging are permitted).
4. Previous treatment with cetuximab, panitumumab, pomalidomide (CC-4047), lenalidomide or thalidomide.
5. Untreated, symptomatic brain metastases (brain imaging not required).
6. Venous thromboembolism ≤ 6 months before day1 of the first cycle.
7. Current congestive heart failure (classes II to IV of the New York Heart Association).
8. Myocardial infarction ≤ 12 months before day1 of the first cycle.
9. Uncontrolled hypertension.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lenalidomide plus cetuximab	cetuximab	Combination therapy of lenalidomide plus cetuximab
lenalidomide	lenalidomide	Single agent therapy of lenalidomide
lenalidomide plus cetuximab	lenalidomide	Combination therapy of lenalidomide plus cetuximab

Primary Outcome Measures

Name	Time	Method
Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period	Up to Day 28 (Cycle 1)	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.
Percentage of Participants With a Response to Treatment During the Proof of Concept Period	week 9 up to week 24	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.

Secondary Outcome Measures

Name	Time	Method
Kaplan-Meier Estimates for Progression Free Survival (PFS)	up to week 24	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.
Kaplan-Meier Estimates for Duration of Response	up to week 24	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.
Percentage of Participants With Disease Control	up to week 24	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.
Kaplan-Meier Estimates for Overall Survival	up to 5.5 years	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.
Participants With Treatment-Emergent Adverse Events (TEAE)	up to week 28	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.

Trial Locations

Locations (17)

ULB Erasme Service de Gastroenterologie; 🇧🇪 Brussels, Belgium

Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica; 🇮🇹 Ancona, Italy

Grand hôpital de Charleroi, Oncologie; 🇧🇪 Charleroi, Belgium

Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie; 🇧🇪 Leuven, Belgium

Klinikum Oldenburg gGmbH Klinik für Innere Medizin II; 🇩🇪 Oldenburg, Niedersachsen, Germany

Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck; 🇮🇹 Milano, Italy

UZ Antwerpen Dept. of Medical Oncology; 🇧🇪 Antwerp, Belgium

Centre Hospitalier Universitaire Sart Tilman Liège; 🇧🇪 Liège, Belgium

Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica; 🇮🇹 Genova, Italy

Algemeen Ziekenhuis Maria Middelares; 🇧🇪 Gent, Belgium

Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos; 🇪🇸 Barcelona, Spain

Akademiska Sjukhuset Onkologkliniken; 🇸🇪 Uppsala, Sweden

Hospital Universitario Marques de Valdecilla Servicio de Oncología; 🇪🇸 Santander, Spain

Östra Sjukhuset Kirurgkliniken; 🇸🇪 Gothenburg, Sweden

Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology; 🇸🇪 Stockholm, Sweden

Hospital Clinico Universitario de Valencia Servicio de Oncologia; 🇪🇸 Valencia, Spain

Flinders Medical Centre, Dept. of Oncology; 🇦🇺 Bedford Park, South Australia, Australia