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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01032291
• Other study ID #: CC-5013-COLO-001
• Secondary ID: 2009-012665-61
• Status: Terminated
• Phase: Phase 2
• First received: December 14, 2009
• Last updated: April 1, 2013
• Start date: December 2009
• Est. completion date: January 2011

Study information

• Verified date: April 2013
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteeSpain: Spanish Agency of MedicinesSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Flinders Medical Centre, Dept. of Oncology	Bedford Park	South 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
Germany	Klinikum Oldenburg gGmbH Klinik für Innere Medizin II	Oldenburg	Niedersachsen
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
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
Sweden	Östra Sjukhuset Kirurgkliniken	Gothenburg
Sweden	Karolinska University Hospital, Solna, Karolinska Institutet Dept of Oncology	Stockholm
Sweden	Akademiska Sjukhuset Onkologkliniken	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Celgene Corporation

Countries where clinical trial is conducted

Australia,  Belgium,  Germany,  Italy,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes