Back to resultsA Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
cetuximab
lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal cancer, Revlimid, Lenalidomide, Cetuximab, Erbitux, KRAS
Eligibility Criteria
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.
Sites / Locations
- Flinders Medical Centre, Dept. of Oncology
- UZ Antwerpen Dept. of Medical Oncology
- ULB Erasme Service de Gastroenterologie
- Grand hôpital de Charleroi, Oncologie
- Algemeen Ziekenhuis Maria Middelares
- Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie
- Centre Hospitalier Universitaire Sart Tilman Liège
- Klinikum Oldenburg gGmbH Klinik für Innere Medizin II
- Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica
- Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica
- Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck
- Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos
- Hospital Universitario Marques de Valdecilla Servicio de Oncología
- Hospital Clinico Universitario de Valencia Servicio de Oncologia
- Östra Sjukhuset Kirurgkliniken
- Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology
- Akademiska Sjukhuset Onkologkliniken
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
lenalidomide plus cetuximab
lenalidomide
Arm Description
Combination therapy of lenalidomide plus cetuximab
Single agent therapy of lenalidomide
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01032291
Brief Title
A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
A business decision not to continue with Phase 2b based on non-safety observations during proof of concept phase.
Study Start Date
December 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Colorectal cancer, Revlimid, Lenalidomide, Cetuximab, Erbitux, KRAS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lenalidomide plus cetuximab
Arm Type
Experimental
Arm Description
Combination therapy of lenalidomide plus cetuximab
Arm Title
lenalidomide
Arm Type
Experimental
Arm Description
Single agent therapy of lenalidomide
Intervention Type
Drug
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Daily oral lenalidomide 25mg on days 1 to 28 of each 28 day cycle
Primary Outcome Measure Information:
Title
Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period
Description
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.
Time Frame
Up to Day 28 (Cycle 1)
Title
Percentage of Participants With a Response to Treatment During the Proof of Concept Period
Description
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.
Time Frame
week 9 up to week 24
Secondary Outcome Measure Information:
Title
Kaplan-Meier Estimates for Progression Free Survival (PFS)
Description
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.
Time Frame
up to week 24
Title
Kaplan-Meier Estimates for Duration of Response
Description
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.
Time Frame
up to week 24
Title
Percentage of Participants With Disease Control
Description
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.
Time Frame
up to week 24
Title
Kaplan-Meier Estimates for Overall Survival
Description
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.
Time Frame
up to 5.5 years
Title
Participants With Treatment-Emergent Adverse Events (TEAE)
Description
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.
Time Frame
up to week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Van Cutsem, M.D., Ph,D
Organizational Affiliation
Universitaire Ziekenhuis Gasthuisberg K.U. Leuven, Belgium
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Josep Tabernero, M.D.
Organizational Affiliation
Hospital Vall d´Hebrón, Servicio de Oncología, Barcelona. Spain
Official's Role
Principal Investigator
Facility Information:
Facility Name
Flinders Medical Centre, Dept. of Oncology
City
Bedford Park
State/Province
South Australia
Country
Australia
Facility Name
UZ Antwerpen Dept. of Medical Oncology
City
Antwerp
Country
Belgium
Facility Name
ULB Erasme Service de Gastroenterologie
City
Brussels
Country
Belgium
Facility Name
Grand hôpital de Charleroi, Oncologie
City
Charleroi
Country
Belgium
Facility Name
Algemeen Ziekenhuis Maria Middelares
City
Gent
Country
Belgium
Facility Name
Universitaire Ziekenhuis Gasthuisberg K.U. Leuven Gastroenterologie, Oncologie
City
Leuven
Country
Belgium
Facility Name
Centre Hospitalier Universitaire Sart Tilman Liège
City
Liège
Country
Belgium
Facility Name
Klinikum Oldenburg gGmbH Klinik für Innere Medizin II
City
Oldenburg
State/Province
Niedersachsen
Country
Germany
Facility Name
Azienda Osperdaliero Universitaria Riuniti Umberto I-GM Lancisi-G. Salesi di Ancona Clinica di Oncologia Medica
City
Ancona
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria San Martino Unità Operativa Oncologia Medica
City
Genova
Country
Italy
Facility Name
Azienda Ospedaliera Niguarda Ca' Grande, Oncologia Medica Falck
City
Milano
Country
Italy
Facility Name
Hospital Vall D'Hebron Servicio de Oncología. Unidad de ensayos clínicos
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Marques de Valdecilla Servicio de Oncología
City
Santander
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia Servicio de Oncologia
City
Valencia
Country
Spain
Facility Name
Östra Sjukhuset Kirurgkliniken
City
Gothenburg
Country
Sweden
Facility Name
Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology
City
Stockholm
Country
Sweden
Facility Name
Akademiska Sjukhuset Onkologkliniken
City
Uppsala
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
24244687
Citation
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.
Results Reference
derived
PubMed Identifier
24244261
Citation
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.
Results Reference
derived
Learn more about this trial
A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer
We'll reach out to this number within 24 hrs