Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Immunological

Combination therapy of lenalidomide plus 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.

cetuximab

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

lenalidomide

Eric Van Cutsem, M.D., Ph,D

Josep Tabernero, M.D.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

Celgene Corporation

Single agent therapy of lenalidomide (25 mg/day) during the Proof of Concept period.

Lenalidomide (Proof of Concept)

Combination therapy of lenalidomide plus cetuximab during both the Safety Lead-in and Proof of Concept periods. Lenalidomide dose of 25 mg/day in combination with cetuximab (IV injections of 400 mg/m\^2 first infusion only, then 250 mg/m\^2 subsequently administered on Days 1, 8, 15, and 22 of each 28-day cycle).

Lenalidomide + Cetuximab (Safety Lead-in and Proof of Concept)

Combination therapy of lenalidomide plus cetuximab during the Safety Lead-in period. Lenalidomide dose of 25 mg/day in combination with cetuximab (IV injections of 400 mg/m\^2 first infusion only, then 250 mg/m\^2 subsequently administered on Days 1, 8, 15, and 22 of each 28-day cycle).

Lenalidomide Plus Cetuximab (Safety Lead-In)

Combination therapy of lenalidomide plus cetuximab during the Proof of Concept period. Lenalidomide dose of 25 mg/day in combination with cetuximab (IV injections of 400 mg/m\^2 first infusion only, then 250 mg/m\^2 subsequently administered on Days 1, 8, 15, and 22 of each 28-day cycle).

Lenalidomide Plus Cetuximab (Proof of Concept)

Total

<= 65 years

>65 years

All baseline measures are reported from the safety population.

Age, Customized

Sex: Female, Male

Caucasian (White)

Other (Not Specified)

Race/Ethnicity, Customized

Hispanic or Latino

Non-Hispanic or Latino

The ECOG scale is as follows:

Grade 0: Fully active, able to carry on all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair.

Eastern Cooperative Oncology Group Performance Status

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

Associate Director, Clinical Trials Disclosure

Lenalidomide Plus Cetuximab (Safety Lead-in)

All participants who took at least one dose of study medication. If a participant discontinued the study prior to completing the entire first cycle for reasons other than a DLT or if ≥7 days of lenalidomide and/or ≥1 dose of cetuximab were missed during the first cycle for reasons other than a DLT, a replacement would be added at that dose level.

Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period

Complete Response

Partial Response

Stable Disease

Progressive Disease

Response Not Evaluable

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).

* Complete response-disappearance of all lesions
* Partial response-30% decrease in the sum of diameters of target lesions from baseline
* Stable disease-neither shrinkage nor increase of lesions.
* Progressive Disease-20% increase in the sum of diameters of target lesions from nadir.

Participants with evidence of objective tumor response have the response confirmed with repeat assessments performed at the next scheduled scan.

Best Overall Response Assessed by an Independent Review Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) During the Proof of Concept Period Prior to Early Study Termination

Participants who took at least one dose of study treatment. Analysis was not performed due to the early termination of the study.

Kaplan-Meier Estimates for Progression Free Survival (PFS)

Kaplan-Meier Estimates for Duration of Response

Percentage of Participants With Disease Control

Kaplan-Meier Estimates for Overall Survival

>=1 TEAE

Serious TEAE

TEAE leading to discontinuing lenalidomide

TEAE leading to discontinuing cetuximab

TEAE leading to reduction/interruption of lenalido

TEAE leading to reduction/interruption of cetuxima

TEAE related to lenalidomide

TEAE related to cetuximab

TEAE NCI CTC grade 3 or higher

TEAE NCI CTC grade 3+ related to lenalidomide

TEAE NCI CTC grade 3+ related to cetuximab

Serious TEAE related to lenalidomide

Serious TEAE related to cetuximab

Participants who took at least one dose of study treatment.

Participants With Treatment-Emergent Adverse Events (TEAE)

Efficacy Evaluable Population. Analysis was not performed due to the early termination of the study.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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