Clinical trial NCT00931840: A Study of EZN-2208 Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma
Official title: A Phase 2 Study of EZN-2208 (PEG-SN38) Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma (mCRC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: EZN-2208 (PEG-SN38)
Lead sponsor: Enzon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-07-02
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Response Rate
timeFrame: 2011
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 2011
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Location #033
state: Arizona
city: Alhambra
country: United States
facility: Location# 042
state: California
city: Bakersfield
country: United States
facility: Location # 043
state: California
city: Fullerton
country: United States
facility: Location# 044
state: California
city: La Jolla
country: United States
facility: Location# 019
state: California
city: Long Beach
country: United States
facility: Location# 046
state: California
city: Los Angeles
country: United States
facility: Location# 053
state: California
city: Northridge
country: United States
facility: Location# 051
state: California
city: Pomona
country: United States
facility: Location# 045
state: California
city: Santa Barbara,
country: United States
facility: Location # 048
state: California
city: Santa Barbara
country: United States
facility: Location # 049
state: California
city: Santa Maria
country: United States
facility: Location# 052
state: California
city: Stanford
country: United States
facility: Location #027
state: California
city: Newark
country: United States
facility: Location# 003
state: Delaware
city: Orlando
country: United States
facility: Location# 047
state: Florida
city: Port St. Lucie
country: United States
facility: Location# 022
state: Florida
city: Marietta
country: United States
facility: Location# 005
state: Georgia
city: Chicago
country: United States
facility: Location# 009
state: Illinois
city: Terre Haute
country: United States
facility: Location #050
state: Indiana
city: Worcester
country: United States
facility: Location# 029
state: Massachusetts
city: Lebanon
country: United States
facility: Location #031
state: New Hampshire
city: Bronx
country: United States
facility: Location# 007
state: New York
city: Buffalo
country: United States
facility: Location # 030
state: New York
city: New York
country: United States
facility: Location# 035
state: New York
city: New York
country: United States
facility: Location# 002
state: New York
city: Chapel Hill
country: United States
facility: Location# 001
state: North Carolina
city: Goldsboro
country: United States
facility: Location# 020
state: North Carolina
city: Winston-Salem
country: United States
facility: Location# 024
state: North Carolina
city: Columbus
country: United States
facility: Location# 008
state: Ohio
city: Lancaster
country: United States
facility: Location# 037
state: Pennsylvania
city: Greenville
country: United States
facility: Location# 018
state: South Carolina
city: Memphis
country: United States
facility: Location# 004
state: Tennessee
city: Houston
country: United States
facility: Location #038
state: Texas
city: Lubbock
country: United States
facility: Location# 011
state: Texas
city: San Antonio
country: United States
facility: Location# 021
state: Texas
city: Ottawa
country: Canada
facility: Location# 076
state: Ontario
city: Toronto
country: Canada
facility: Location # 079
state: Ontario
city: Montreal
country: Canada
facility: Location# 077
state: Quebec
city: Montreal
country: Canada
facility: Location# 074
state: Quebec
city: Rimouski
country: Canada
facility: Location# 055
state: Quebec
city: Tel-Aviv
country: Israel
facility: Location# 066
state: Central District
city: Kfar Saba
country: Israel
facility: Location# 071
state: Sharon
city: Beer Sheva
country: Israel
facility: Location# 072
state: South District
city: Be'er Ya'aqov
country: Israel
facility: Location# 068
city: Haifa
country: Israel
facility: Location# 067
city: Jerusalem District
country: Israel
facility: Location# 073
city: Tel Hashomer
country: Israel
facility: Location# 069
city: Tel-Aviv
country: Israel
facility: Location# 070
city: Leiden
country: Netherlands
facility: Location# 041
state: NL
city: Rotterdam
country: Netherlands
facility: Location # 040
state: The Netherlands
city: Dorchester
country: United Kingdom
facility: Location #065
state: Dorset
city: London
country: United Kingdom
facility: Location # 083
state: England
city: London
country: United Kingdom
facility: Location# 057
state: Greater London
city: London
country: United Kingdom
facility: Location# 054-2
state: Greater London
city: London
country: United Kingdom
facility: Location #061
state: Greater London
city: Manchester
country: United Kingdom
facility: Location# 064
state: Greater Manchester
city: Edinburgh
country: United Kingdom
facility: Location# 056
state: Scotland
city: Glasgow
country: United Kingdom
facility: Location# 062
state: Scotland
city: Sutton
country: United Kingdom
facility: Location# 054
state: Surrey
city: Leeds
country: United Kingdom
facility: Location# 063
state: West Yorkshire
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Richard M. Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
References: