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

This study has been terminated.
(A business decision not to continue with Phase 2b based on non-safety observations during proof of concept phase.)
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01032291
First received: December 14, 2009
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: cetuximab
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period [ Time Frame: Up to Day 28 (Cycle 1) ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: week 9 up to week 24 ] [ Designated as safety issue: No ]

    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:
  • Kaplan-Meier Estimates for Progression Free Survival (PFS) [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to 5.5 years ] [ Designated as safety issue: No ]

    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) [ Time Frame: up to week 28 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 51
Study Start Date: December 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Erbitux
Drug: lenalidomide
Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle
Other Name: 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 Name: Revlimid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01032291

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

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01032291     History of Changes
Other Study ID Numbers: CC-5013-COLO-001, 2009-012665-61
Study First Received: December 14, 2009
Results First Received: April 1, 2013
Last Updated: April 1, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency

Keywords provided by Celgene Corporation:
Colorectal cancer
Revlimid
Lenalidomide
Cetuximab
Erbitux
KRAS

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014