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

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

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.

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: EZN-2208, Cetuximab and Irinotecan

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.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response Rate	2011

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS)	2011

Collaborators and Investigators

• Sponsor: Enzon Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Richard M. Goldberg, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): January 1, 2012

Study Registration Dates

• First Submitted: June 30, 2009
• First Submitted That Met QC Criteria: June 30, 2009
• First Posted (Estimate): July 2, 2009

Study Record Updates

• Last Update Posted (Estimate): September 20, 2011
• Last Update Submitted That Met QC Criteria: September 19, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: EZN-2208 (PEG-SN38)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: EZN-2208-04