A Study of EZN-2208 Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma

NCT ID: NCT00931840

Last Updated: 2011-09-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2012-01-31

Brief Summary

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This is a Phase 2, multicenter, multiple-arm, open-label study to evaluate the efficacy, safety, and tolerability of EZN-2208. EZN-2208 will be administered as a single agent in patients with K-RAS mutations in the tumors. Patients with wild type K-RAS in tumors will be randomized to EZN-2208 + cetuximab or to standard of care (Camptosar® + cetuximab), patients must have failed regimens containing irinotecan (Camptosar®, CPT-11), oxaliplatin (Eloxatin®), and fluoropyrimidine.

After discontinuation of study treatment, patients will receive care as considered appropriate by the investigator. Patients will continue to be followed for disease progression, subsequent anticancer therapy, and survival.

Detailed Description

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EZN-2208 will be administered by i.v. infusion weekly for 3 weeks in 4-week cycles. The cetuximab infusion will be administered before the EZN-2208 (Arm B) or irinotecan (Arm C) infusion. Study treatment will be continued until evidence of disease progression, unacceptable toxicity, or withdrawal of the patient's consent for participation in the study.

Approximately 220 patients will be enrolled in this study: approximately 100 patients in the K-RAS mutated arm and approximately 120 patients in the wild-type K-RAS arm.

Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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EZN-2208

EZN-2208 will be administered as an i.v. infusion on weekly basis for 3 weeks and repeated every 28 days.

PLEASE NOTE THAT ENROLLMENT IN EXPERIMENTAL ARM (ARM A) IS COMPLETE. NO NEW PATIENT IN THIS ARM IS ALLOWED TO ENROLL.

Group Type EXPERIMENTAL

EZN-2208, Cetuximab and Irinotecan

Intervention Type DRUG

Patients with mutated K RAS tumors will be treated with single-agent EZN-2208 (Arm A). PLEASE NOTE THAT ENROLLMENT IN EXPERIMENTAL ARM (ARM A) IS COMPLETE. NO NEW PATIENT IN THIS ARM IS ALLOWED TO ENROLL.

Patients with wild-type K-RAS tumors will be randomly assigned in a 2:1 ratio to EZN-2208 + cetuximab (Arm B) or the benchmark of irinotecan + cetuximab (Arm C).

Cetuximab + EZN-2208

Cetuximab will be administered as an i.v. infusion on weekly basis. EZN-2208 administered as i.v. infusion on weekly basis for 3 weeks and repeated every 28 days.

Group Type EXPERIMENTAL

EZN-2208, Cetuximab and Irinotecan

Intervention Type DRUG

Patients with mutated K RAS tumors will be treated with single-agent EZN-2208 (Arm A). PLEASE NOTE THAT ENROLLMENT IN EXPERIMENTAL ARM (ARM A) IS COMPLETE. NO NEW PATIENT IN THIS ARM IS ALLOWED TO ENROLL.

Patients with wild-type K-RAS tumors will be randomly assigned in a 2:1 ratio to EZN-2208 + cetuximab (Arm B) or the benchmark of irinotecan + cetuximab (Arm C).

Irinotecan + cetuximab

Cetuximab will be administered weekly as an i.v. infusion. Irinotecan will be administered as an i.v. infusion on Weeks 1 and 2 and repeated every 3 weeks.

Group Type ACTIVE_COMPARATOR

EZN-2208, Cetuximab and Irinotecan

Intervention Type DRUG

Patients with mutated K RAS tumors will be treated with single-agent EZN-2208 (Arm A). PLEASE NOTE THAT ENROLLMENT IN EXPERIMENTAL ARM (ARM A) IS COMPLETE. NO NEW PATIENT IN THIS ARM IS ALLOWED TO ENROLL.

Patients with wild-type K-RAS tumors will be randomly assigned in a 2:1 ratio to EZN-2208 + cetuximab (Arm B) or the benchmark of irinotecan + cetuximab (Arm C).

Interventions

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EZN-2208, Cetuximab and Irinotecan

Patients with mutated K RAS tumors will be treated with single-agent EZN-2208 (Arm A). PLEASE NOTE THAT ENROLLMENT IN EXPERIMENTAL ARM (ARM A) IS COMPLETE. NO NEW PATIENT IN THIS ARM IS ALLOWED TO ENROLL.

Patients with wild-type K-RAS tumors will be randomly assigned in a 2:1 ratio to EZN-2208 + cetuximab (Arm B) or the benchmark of irinotecan + cetuximab (Arm C).

Intervention Type DRUG

Other Intervention Names

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Irinotecan, (CPT 11),(Camptosar®) Erbitux (cetuximab)

Eligibility Criteria

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Inclusion Criteria

* Patients must meet all of the following criteria to be eligible for enrollment in the study.

1. Histologically confirmed CRC adenocarcinoma that is metastatic or locally recurrent CRC that is nonresectable
2. Patients must agree to genetic testing of the original or metastatic CRC tumor biopsy tissue for K-RAS mutational status.
3. Disease progression
4. Previous therapy with irinotecan, oxaliplatin, and fluoropyrimidine either alone or in any combination(s). Patients must have radiographically documented progressive disease while receiving, or within 3 months of receiving, these agents alone or in combination.
5. No more than 2 prior cytotoxic chemotherapy regimens.
6. Age 18 years or older
7. Measurable disease by RECIST Version 1.1
8. ECOG performance status of 0 or 1
9. Adequate bone marrow, renal, and hepatic function

Exclusion Criteria

1. Known chronic infectious disease
2. Major surgery within 3 weeks before study start
3. Known or suspected brain metastases requiring intervention with steroids and/or radiation therapy.
4. Prior chemotherapy, immunotherapy, non-investigational agent, or other therapy used to treat the cancer within 3 weeks before the scheduled administration of EZN-2208
5. History of other primary cancer within 5 years of enrollment, unless

1. Curatively resected non-melanomatous skin cancer, or
2. Curatively resected cervical cancer
6. Lack of recovery to Grade 1 from any reversible side effects related to the administration of an investigational agent, or other prior treatments for the cancer
7. Any condition such as uncontrollable diabetes, uncontrollable hypertension, or active infection.
8. Current participation in another clinical study with an investigational agent and/or use of an investigational drug (not including investigational use of an approved drug) in the 30 days before the first administration of EZN-2208
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Enzon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard M. Goldberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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Location #033

Tucson, Arizona, United States

Site Status

Location# 042

Alhambra, California, United States

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Location # 043

Bakersfield, California, United States

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Location# 044

Fullerton, California, United States

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Location# 019

La Jolla, California, United States

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Location# 046

Long Beach, California, United States

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Location# 053

Los Angeles, California, United States

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Location# 051

Northridge, California, United States

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Location# 045

Pomona, California, United States

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Location # 048

Santa Barbara, California, United States

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Location # 049

Santa Barbara, California, United States

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Location# 052

Santa Maria, California, United States

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Location #027

Stanford, California, United States

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Location# 003

Newark, Delaware, United States

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Location# 047

Orlando, Florida, United States

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Location# 022

Port Saint Lucie, Florida, United States

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Location# 005

Marietta, Georgia, United States

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Location# 009

Chicago, Illinois, United States

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Location #050

Terre Haute, Indiana, United States

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Location# 029

Worcester, Massachusetts, United States

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Location #031

Lebanon, New Hampshire, United States

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Location # 030

Buffalo, New York, United States

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Location# 035

New York, New York, United States

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Location# 002

New York, New York, United States

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Location# 007

The Bronx, New York, United States

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Location# 001

Chapel Hill, North Carolina, United States

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Location# 020

Goldsboro, North Carolina, United States

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Location# 024

Winston-Salem, North Carolina, United States

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Location# 008

Columbus, Ohio, United States

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Location# 037

Lancaster, Pennsylvania, United States

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Location# 018

Greenville, South Carolina, United States

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Location# 004

Memphis, Tennessee, United States

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Location #038

Houston, Texas, United States

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Location# 011

Lubbock, Texas, United States

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Location# 021

San Antonio, Texas, United States

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Location# 076

Ottawa, Ontario, Canada

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Location # 079

Toronto, Ontario, Canada

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Location# 077

Montreal, Quebec, Canada

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Location# 074

Montreal, Quebec, Canada

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Location# 055

Rimouski, Quebec, Canada

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Location# 066

Tel-Aviv, Central District, Israel

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Location# 071

Kfar Saba, Sharon, Israel

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Location# 072

Beersheba, South District, Israel

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Location# 068

Be’er Ya‘aqov, , Israel

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Location# 067

Haifa, , Israel

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Location# 073

Jerusalem District, , Israel

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Location# 070

Tel Aviv, , Israel

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Location# 069

Tel Litwinsky, , Israel

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Location# 041

Leiden, NL, Netherlands

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Location # 040

Rotterdam, The Netherlands, Netherlands

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Location #065

Dorchester, Dorset, United Kingdom

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Location # 083

London, England, United Kingdom

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Location# 057

London, Greater London, United Kingdom

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Location# 054-2

London, Greater London, United Kingdom

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Location #061

London, Greater London, United Kingdom

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Location# 064

Manchester, Greater Manchester, United Kingdom

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Location# 056

Edinburgh, Scotland, United Kingdom

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Location# 062

Glasgow, Scotland, United Kingdom

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Location# 054

Sutton, Surrey, United Kingdom

Site Status

Location# 063

Leeds, West Yorkshire, United Kingdom

Site Status

Countries

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United States Canada Israel Netherlands United Kingdom

Other Identifiers

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EZN-2208-04

Identifier Type: -

Identifier Source: org_study_id

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