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

Metastatic Colorectal Cancer Clinical Trial

Official title:

A Phase 2 Study of EZN-2208 (PEG-SN38) Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma (mCRC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00931840
• Other study ID #: EZN-2208-04
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 30, 2009
• Last updated: September 19, 2011
• Start date: June 2009
• Est. completion date: January 2012

Study information

• Verified date: September 2011
• Source: Enzon Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 220
• Est. completion date: January 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

• Patients meeting any of the following exclusion criteria will not be eligible for enrollment.

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

Study Design

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

Related Conditions & MeSH terms

• Metastatic Colorectal Cancer

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
Canada	Location# 074	Montreal	Quebec
Canada	Location# 077	Montreal	Quebec
Canada	Location# 076	Ottawa	Ontario
Canada	Location# 055	Rimouski	Quebec
Canada	Location # 079	Toronto	Ontario
Israel	Location# 068	Be'er Ya`aqov
Israel	Location# 072	Beer Sheva	South District
Israel	Location# 067	Haifa
Israel	Location# 073	Jerusalem District
Israel	Location# 071	Kfar Saba	Sharon
Israel	Location# 069	Tel Hashomer
Israel	Location# 066	Tel-Aviv	Central District
Israel	Location# 070	Tel-Aviv
Netherlands	Location# 041	Leiden	NL
Netherlands	Location # 040	Rotterdam	The Netherlands
United Kingdom	Location #065	Dorchester	Dorset
United Kingdom	Location# 056	Edinburgh	Scotland
United Kingdom	Location# 062	Glasgow	Scotland
United Kingdom	Location# 063	Leeds	West Yorkshire
United Kingdom	Location # 083	London	England
United Kingdom	Location #061	London	Greater London
United Kingdom	Location# 054-2	London	Greater London
United Kingdom	Location# 057	London	Greater London
United Kingdom	Location# 064	Manchester	Greater Manchester
United Kingdom	Location# 054	Sutton	Surrey
United States	Location# 042	Alhambra	California
United States	Location # 043	Bakersfield	California
United States	Location# 007	Bronx	New York
United States	Location # 030	Buffalo	New York
United States	Location# 001	Chapel Hill	North Carolina
United States	Location# 009	Chicago	Illinois
United States	Location# 008	Columbus	Ohio
United States	Location# 044	Fullerton	California
United States	Location# 020	Goldsboro	North Carolina
United States	Location# 018	Greenville	South Carolina
United States	Location #038	Houston	Texas
United States	Location# 019	La Jolla	California
United States	Location# 037	Lancaster	Pennsylvania
United States	Location #031	Lebanon	New Hampshire
United States	Location# 046	Long Beach	California
United States	Location# 053	Los Angeles	California
United States	Location# 011	Lubbock	Texas
United States	Location# 005	Marietta	Georgia
United States	Location# 004	Memphis	Tennessee
United States	Location# 002	New York	New York
United States	Location# 035	New York	New York
United States	Location# 003	Newark	Delaware
United States	Location# 051	Northridge	California
United States	Location# 047	Orlando	Florida
United States	Location# 045	Pomona	California
United States	Location# 022	Port St. Lucie	Florida
United States	Location# 021	San Antonio	Texas
United States	Location # 049	Santa Barbara	California
United States	Location # 048	Santa Barbara,	California
United States	Location# 052	Santa Maria	California
United States	Location #027	Stanford	California
United States	Location #050	Terre Haute	Indiana
United States	Location #033	Tucson	Arizona
United States	Location# 024	Winston-Salem	North Carolina
United States	Location# 029	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Enzon Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate		2011	Yes
Secondary	Progression Free Survival (PFS)		2011	Yes