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

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:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride Cetuximab

U.S. FDA Resources

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

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

Show 60 Study Locations

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:

Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases

Rectal Diseases
Irinotecan
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013