A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer
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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 |
- 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.
- 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 |
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.
Contacts and 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 | |
| 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
| 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 Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Cetuximab Lenalidomide Thalidomide |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013