Lenalidomide and Cetuximab in Treating Patients With Metastatic Colorectal Cancer

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Terminated

CT.gov ID

NCT01126450

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving lenalidomide together with cetuximab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lenalidomide when given together with cetuximab in treating patients with metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer Rectal Cancer	Drug: lenalidomide Biological: cetuximab Other: mutation analysis Other: polymerase chain reaction Genetic: polymorphism analysis	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose (MTD).

SECONDARY OBJECTIVES:

To further explore the safety and efficacy profile.

OUTLINE:

This is a dose-escalation study of lenalidomide.

Patients receive oral lenalidomide once daily on days 1-28 and cetuximab IV once weekly over 1-2 hours on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open-Label Study To Determine The Maximum Tolerated Dose (Mtd) Of The Combination Of Lenalidomide And Cetuximab, And To Evaluate The Efficacy Of This Combination In Subjects With Wild Type K-Ras Metastatic Colorectal Carcinoma

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral lenalidomide once daily on days 1-28 and cetuximab IV once weekly over 1-2 hours on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide Given orally Other Names: CC-5013 IMiD-1 Revlimid Biological: cetuximab Given IV Other Names: Anti-EGFR Monoclonal Antibody C225 C225 monoclonal antibody IMC-C225 MOAB C225 monoclonal antibody C225 Other: mutation analysis Correlative studies Other: polymerase chain reaction Correlative studies Other Names: PCR Genetic: polymorphism analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Arm I

Drug: lenalidomide

Given orally

Other Names:

CC-5013

IMiD-1

Revlimid

Biological: cetuximab

Given IV

Other Names:

Anti-EGFR Monoclonal Antibody

C225

C225 monoclonal antibody

IMC-C225

MOAB C225

monoclonal antibody C225

Other: mutation analysis

Correlative studies

Other: polymerase chain reaction

Correlative studies

Other Names:

PCR

Genetic: polymorphism analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Safety / Tolerability (type, frequency, severity, and relationship of adverse events to study drug) [Courses repeat every 28 days in the absence of unacceptable toxicity.]

Secondary Outcome Measures

Time to progression of disease [Courses repeat every 28 days in the absence of disease progression .]
Tumor response according to RECIST [at the end of Cycle 2 and every 56 days thereafter until tumor progression]
Lab correlatives (FCGRIIa and FCGRIIIa polymorphisms, K-Ras and B-Raf mutations) [Tissue collection less than or equal to 28 days prior to day 1 of therapy]
FCGR2a and FCGR3a polymorphisms, K-Ras and B-Raf mutations in patient specimens (paraffin embedded formaldehyde fixed tissues) will be identified.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion

Wild type metastatic colorectal cancer that failed (progressed, refused or not tolerated) on at least two treatment regimens including a fluoropyrimidine, oxaliplatin and irinotecan with or without bevacizumab
At least 28 days must have lapsed since completion of prior chemotherapy
Subjects must understand and voluntarily sign an informed consent document
Subjects must be able to adhere to the study visit schedule and other protocol requirements
Histological or cytological diagnosis of colorectal carcinoma
Radiographic or clinical evidence of a measurable disease (by RECIST criteria)
Subjects must have received prior treatment with at least 2 prior regimens of therapy
ECOG performance status of =< 1
Anticipated survival >= 3 months
Must agree to also take low dose aspirin (or other anticoagulation if unable to take ASA) while receiving study drug and for 30 days after study drug is discontinued
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing
Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy

Exclusion

Pregnant or lactating females
CrCl < 50 mL/min by Cock-Croft and Gault
Any serious medical condition or psychiatric illness that places the subject at an unacceptable risk for study participation or would prevent the subject from signing the informed consent
Use of any cytotoxic chemotherapy within 28 days of study Day 1
Use of therapeutic radiation =< 14 days prior to study Day 1
Use of thalidomide, or structurally related compounds or biologic response modifier therapy within 14 days of study Day 1
Prior desquamating rash while taking thalidomide, or structurally related compound therapy
Prior >= Grade 2 allergic reaction to thalidomide or structurally related compounds
Any prior use of Lenalidomide
Subjects may have received prior thalidomide
Known or suspected brain metastases
Concurrent use or anticipated use of any other anti-cancer agents (except for stable dose steroid use for control of metastases symptoms) during participation in this study
Absolute Neutrophil Count =< 1500/mm^{3 (or 1.5 X10}9/L)
Platelet Count =< 100,000/mm^{3 (or 100 X 10}9/L)
Hemoglobin < 8.0 g/dL
Total Bilirubin > 2.0mg/dL
Alanine Aminotransferase (ALT/SGPT) >= 3 x upper limit of normal (ULN)
Aspartate Aminotransferase (AST/SGOT) >= 3 x upper limit of normal (ULN)
Peripheral neuropathy >= Grade 2
Active infection
Subjects with an infection that is amenable to curative treatment may be eligible for screening once the infection has been treated, cured and not recurred for at least 14 days
Uncontrolled hyper- or hypo- calcemia, glycosemia or thyroidism
Arterial or venous thrombotic event in the preceding six months
Known history of HIV infection
Active viral hepatitis who is on active treatment
No other malignancies, other than previously treated non-melanoma skin cancer or carcinoma insitu of the cervix or breast