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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Enzon Pharmaceuticals, Inc..
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Enzon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00931840
First received: June 30, 2009
Last updated: September 19, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: EZN-2208, Cetuximab and Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of EZN-2208 (PEG-SN38) Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma (mCRC)

Resource links provided by NLM:


Further study details as provided by Enzon Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 2011 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 220
Study Start Date: June 2009
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

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).

Other Names:
  • Irinotecan, (CPT 11),(Camptosar®)
  • Erbitux (cetuximab)
Experimental: 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.
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).

Other Names:
  • Irinotecan, (CPT 11),(Camptosar®)
  • Erbitux (cetuximab)
Active Comparator: 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.
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).

Other Names:
  • Irinotecan, (CPT 11),(Camptosar®)
  • Erbitux (cetuximab)

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931840

  Hide Study Locations
Locations
United States, Arizona
Location #033
Tucson, Arizona, United States, 85724-5024
United States, California
Location# 042
Alhambra, California, United States, 91801
Location # 043
Bakersfield, California, United States, 93309
Location# 044
Fullerton, California, United States, 92835
Location# 019
La Jolla, California, United States, 92093-0698
Location# 046
Long Beach, California, United States, 90813
Location# 053
Los Angeles, California, United States, 90095
Location# 051
Northridge, California, United States, 91235
Location# 045
Pomona, California, United States, 91767
Location # 049
Santa Barbara, California, United States, 93105
Location # 048
Santa Barbara,, California, United States, 93105
Location# 052
Santa Maria, California, United States, 93454
Location #027
Stanford, California, United States, 94305
United States, Delaware
Location# 003
Newark, Delaware, United States, 19718
United States, Florida
Location# 047
Orlando, Florida, United States, 32804
Location# 022
Port St. Lucie, Florida, United States, 34952
United States, Georgia
Location# 005
Marietta, Georgia, United States, 30060
United States, Illinois
Location# 009
Chicago, Illinois, United States, 60611-2927
United States, Indiana
Location #050
Terre Haute, Indiana, United States, 47802
United States, Massachusetts
Location# 029
Worcester, Massachusetts, United States, 01655
United States, New Hampshire
Location #031
Lebanon, New Hampshire, United States, 03756
United States, New York
Location# 007
Bronx, New York, United States, 10461
Location # 030
Buffalo, New York, United States, 14263
Location# 002
New York, New York, United States, 10016
Location# 035
New York, New York, United States, 10003
United States, North Carolina
Location# 001
Chapel Hill, North Carolina, United States, 27514
Location# 020
Goldsboro, North Carolina, United States, 27534
Location# 024
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Location# 008
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Location# 037
Lancaster, Pennsylvania, United States, 17605
United States, South Carolina
Location# 018
Greenville, South Carolina, United States, 29615
United States, Tennessee
Location# 004
Memphis, Tennessee, United States, 38138
United States, Texas
Location #038
Houston, Texas, United States, 77584
Location# 011
Lubbock, Texas, United States, 79410
Location# 021
San Antonio, Texas, United States, 78229
Canada, Ontario
Location# 076
Ottawa, Ontario, Canada, K1H 8L6
Location # 079
Toronto, Ontario, Canada, M4C3E7
Canada, Quebec
Location# 074
Montreal, Quebec, Canada, H3T 1E2
Location# 077
Montreal, Quebec, Canada, H2W 1S6
Location# 055
Rimouski, Quebec, Canada, G5L 5T1
Israel
Location# 066
Tel-Aviv, Central District, Israel, 69710
Location# 071
Kfar Saba, Sharon, Israel, 44281
Location# 072
Beer Sheva, South District, Israel, 84101
Location# 068
Be'er Ya`aqov, Israel, 70300
Location# 067
Haifa, Israel, 31096
Location# 073
Jerusalem District, Israel, 91120
Location# 069
Tel Hashomer, Israel, 52621
Location# 070
Tel-Aviv, Israel, 64239
Netherlands
Location# 041
Leiden, NL, Netherlands, 2333ZA
Location # 040
Rotterdam, The Netherlands, Netherlands
United Kingdom
Location #065
Dorchester, Dorset, United Kingdom, DT1 2JY
Location # 083
London, England, United Kingdom, W8 8RF
Location# 054-2
London, Greater London, United Kingdom, SW3 6JJ
Location# 057
London, Greater London, United Kingdom, SE1 7EH
Location #061
London, Greater London, United Kingdom, W12 0HS
Location# 064
Manchester, Greater Manchester, United Kingdom, M20 4BX
Location# 056
Edinburgh, Scotland, United Kingdom, EH4 2XU
Location# 062
Glasgow, Scotland, United Kingdom, G12 0YN
Location# 054
Sutton, Surrey, United Kingdom, SM2 5PT
Location# 063
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Sponsors and Collaborators
Enzon Pharmaceuticals, Inc.
Investigators
Principal Investigator: Richard M. Goldberg, MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Enzon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00931840     History of Changes
Other Study ID Numbers: EZN-2208-04
Study First Received: June 30, 2009
Last Updated: September 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Enzon Pharmaceuticals, Inc.:
EZN-2208 (PEG-SN38)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Irinotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014