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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: cetuximab; Drug: lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Bedford Park, South Australia, Australia
      • Flinders Medical Centre, Dept. of Oncology
• Belgium
  • Antwerp, Belgium
    • UZ Antwerpen Dept. of Medical Oncology
  • Brussels, Belgium
    • ULB Erasme Service de Gastroenterologie
  • Charleroi, Belgium
    • Grand hôpital de Charleroi, Oncologie
  • Gent, Belgium
    • Algemeen ziekenhuis Maria Middelares
  • Leuven, Belgium
    • Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie
  • Liège, Belgium
    • Centre Hospitalier Universitaire Sart Tilman Liège
• Germany
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany
      • Klinikum Oldenburg gGmbH Klinik für Innere Medizin II
• Italy
  • Ancona, Italy
    • Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica
  • Genova, Italy
    • Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica
  • Milano, Italy
    • Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck
• Spain
  • Barcelona, Spain
    • Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla Servicio de Oncología
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia Servicio de Oncologia
• Sweden
  • Gothenburg, Sweden
    • Östra Sjukhuset Kirurgkliniken
  • Stockholm, Sweden
    • Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology
  • Uppsala, Sweden
    • Akademiska Sjukhuset Onkologkliniken

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lenalidomide plus cetuximab; Combination therapy of lenalidomide plus cetuximab	Drug: cetuximab; 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.; Other Names: Erbitux; Drug: lenalidomide; Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle; Other Names: Revlimid
Experimental: lenalidomide; Single agent therapy of lenalidomide	Drug: lenalidomide; Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle; Other Names: Revlimid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene Corporation
• Investigators: Principal Investigator: Eric Van Cutsem, M.D., Ph,D, Universitaire Ziekenhuis Gasthuisberg K.U. Leuven, Belgium; Principal Investigator: Josep Tabernero, M.D., Hospital Vall d´Hebrón, Servicio de Oncología, Barcelona. Spain

Publications and helpful links

General Publications

• Gandhi AK, Shi T, Li M, Jungnelius U, Romano A, Tabernero J, Siena S, Schafer PH, Chopra R. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients. PLoS One. 2013 Nov 11;8(11):e80437. doi: 10.1371/journal.pone.0080437. eCollection 2013.
• Siena S, Van Cutsem E, Li M, Jungnelius U, Romano A, Beck R, Bencardino K, Elez ME, Prenen H, Sanchis M, Sartore-Bianchi A, Tejpar S, Gandhi A, Shi T, Tabernero J. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. PLoS One. 2013 Nov 11;8(11):e62264. doi: 10.1371/journal.pone.0062264. eCollection 2013.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: December 14, 2009
• First Submitted That Met QC Criteria: December 14, 2009
• First Posted (Estimate): December 15, 2009

Study Record Updates

• Last Update Posted (Estimate): May 21, 2013
• Last Update Submitted That Met QC Criteria: April 1, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Colorectal cancer; Lenalidomide; Cetuximab; KRAS; Erbitux; Revlimid
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Cetuximab
• Other Study ID Numbers: CC-5013-COLO-001; 2009-012665-61 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No