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

NCT01032291 | Terminated Phase 2 Results

• 2 other identifiers: CC-5013-COLO-0012009-012665-61
• Study Type: interventional
• Target: 51
• Locations: 6 countries
• Sites: 17

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.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; Revlimid; Lenalidomide; Cetuximab; Erbitux; KRAS

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Kaplan-Meier Estimates for Progression Free Survival (PFS)

  up to week 24

• Kaplan-Meier Estimates for Duration of Response

  up to week 24

• Percentage of Participants With Disease Control

  up to week 24

• Kaplan-Meier Estimates for Overall Survival

  up to 5.5 years

• Participants With Treatment-Emergent Adverse Events (TEAE)

  up to week 28

Study Arms (2)

lenalidomide plus cetuximab

EXPERIMENTAL

Combination therapy of lenalidomide plus cetuximab

Drug: cetuximab; Drug: lenalidomide

lenalidomide

EXPERIMENTAL

Single agent therapy of lenalidomide

Drug: lenalidomide

Interventions

cetuximab DRUG

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.

Also known as: Erbitux

lenalidomide plus cetuximab

lenalidomide DRUG

Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle

Also known as: Revlimid

lenalidomide; lenalidomide plus cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (17)

Flinders Medical Centre, Dept. of Oncology

Bedford Park, South Australia, Australia

Location

UZ Antwerpen Dept. of Medical Oncology

Antwerp, Belgium

Location

ULB Erasme Service de Gastroenterologie

Brussels, Belgium

Location

Grand hôpital de Charleroi, Oncologie

Charleroi, Belgium

Location

Algemeen Ziekenhuis Maria Middelares

Ghent, Belgium

Location

Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie

Leuven, Belgium

Location

Centre Hospitalier Universitaire Sart Tilman Liège

Liège, Belgium

Location

Klinikum Oldenburg gGmbH Klinik für Innere Medizin II

Oldenburg, Lower Saxony, Germany

Location

Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica

Ancona, Italy

Location

Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica

Genova, Italy

Location

Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck

Milan, Italy

Location

Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos

Barcelona, Spain

Location

Hospital Universitario Marques de Valdecilla Servicio de Oncología

Santander, Spain

Location

Hospital Clinico Universitario de Valencia Servicio de Oncologia

Valencia, Spain

Location

Östra Sjukhuset Kirurgkliniken

Gothenburg, Sweden

Location

Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology

Stockholm, Sweden

Location

Akademiska Sjukhuset Onkologkliniken

Uppsala, Sweden

Location

Related Publications (2)

• 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.

  PMID: 24244687 DERIVED

• 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.

  PMID: 24244261 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Lenalidomide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Enrollment stopped prematurely due to lack of efficacy and failure to achieve the planned response objective.

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2009
• First Posted: December 15, 2009
• Study Start: December 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: May 21, 2013
• Results First Posted: May 21, 2013

Record last verified: 2013-04

Locations

AU (1); DE (1); SE (3); BE (6); IT (3); ES (3)