Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Patients With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFr Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ImClone LLC
ClinicalTrials.gov Identifier:
NCT00503685
First received: July 17, 2007
Last updated: October 12, 2011
Last verified: October 2011
  Purpose

Patients with mCRC who have progressed on a prior Anti-EGFr regimen randomized to receive IMC-A12 monotherapy or combination therapy with cetuximab to assess response, survival, durations of response, safety and tolerability as well as pharmacodynamics of IMC-A12 and cetuximab


Condition Intervention Phase
Colorectal Cancer
Biological: IMC-A12
Biological: cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Clinical Trial of IMC-A12, as a Single Agent or in Combination With Cetuximab, in Patients With Metastatic Colorectal Cancer With Disease Progression on Prior Anti-EGFR Therapy

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Duration of stable disease (SD) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Duration of Overall response [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (AEs) [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]
  • Summary Listing of Participants Reporting Treatment-Emergent Severe Adverse Events (SAEs) [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) [ Time Frame: Weeks 1 (Initial dose), Week 1 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6) ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin) [ Time Frame: Weeks 1 (Initial dose), Week 1 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6) ] [ Designated as safety issue: No ]
  • Area under Serum Concentration (AUC) [ Time Frame: Weeks 1 (Initial dose), Week 1 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6) ] [ Designated as safety issue: No ]
  • Potential associations between KRAS mutations and response rate (cetuximab) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Evaluate tumors for expression of Type I IGF receptors (IGF-IR), IGF binding proteins (IGFBP2, IGFBP3), and related signaling molecules, and potential association [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Evaluate tumors for expression of Type I IGF receptors (IGF-IR), IGF binding proteins (IGFBP2, IGFBP3), and related signaling molecules, and assess potential association [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: June 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-A12
Administerd every 2 weeks
Biological: IMC-A12
10 mg/kg intravenous (I.V.) infusion every 2 weeks.
Other Name: Cixutumumab
Experimental: IMC-A12 + cetuximab
Administerd every 2 weeks
Biological: IMC-A12
10 mg/kg intravenous (I.V.) infusion every 2 weeks.
Other Name: Cixutumumab
Biological: cetuximab
Patients will receive cetuximab 500 mg/m2 I.V. over 2 hours every 2 weeks.
Other Name: Erbitux®
Experimental: IMC-A12 + cetuximab (KRAS wild type)
Participants who have experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression are enrolled in this arm.
Biological: IMC-A12
10 mg/kg intravenous (I.V.) infusion every 2 weeks.
Other Name: Cixutumumab
Biological: cetuximab
Patients will receive cetuximab 500 mg/m2 I.V. over 2 hours every 2 weeks.
Other Name: Erbitux®

  Eligibility

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

Inclusion Criteria

  • The patient has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies
  • The patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
  • The patient has clinical documentation of disease progression during treatment or within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or planned treatment break will not be regarded as adequate evidence of disease progression and such patients will not be eligible for this trial
  • The patient has received at least one prior standard and/or investigational regimen for metastatic disease
  • The patient is age ≥ 18 years
  • The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (Karnofsky ≥ 80%)
  • The patient has adequate hematologic function as defined by an absolute neutrophil count ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/μL
  • The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN),* and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
  • The patient has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have an INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or invading the rectal lumen, or known varices)
  • The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above the ULN, as well as urine protein ≤ 1+ on urine dipstick or routine urinalysis (if urine dipstick/routine UA indicates ≥ 2+ protein, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study)
  • The patient has fasting serum glucose < 120 mg/dL or below the ULN
  • The patient has a life expectancy of > 3 months
  • Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • The patient has the ability to understand and the willingness to sign a written informed consent document
  • The patient has a tumor that is KRAS wild-type (absence of mutations at codon 12 or 13, as determined by the DxS K-RAS Mutation Kit [PCR-based analysis]).
  • The patient experienced either a confirmed partial response or stable disease of ≥ 24 weeks duration during prior treatment with a cetuximab- or panitumumab-containing regimen *Except for patients with UGT1A1 promoter polymorphism, ie, Gilbert syndrome, confirmed by genotyping or Invader®UGT1A1 Molecular Assay prior to enrollment. Patients enrolled with Gilbert Syndrome must have a total bilirubin ≤ 3 x ULN. If the patient has liver metastases, total bilirubin must be ≤ 3 x ULN.

Exclusion Criteria

  • The patient has received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to NCI-CTCAE Version 3.0 grade ≤ 2.
  • The patient is receiving any other investigational agent(s).
  • The patient has a history of treatment with other agents targeting the IGFR.
  • The patient has known brain or leptomeningeal metastases.
  • The patient has a history of primary central nervous system tumors, seizures not well controlled with standard medical therapy, or history of stroke within 6 months prior to randomization.
  • The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12 (cixutumumab).
  • The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.
  • The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • The patient is pregnant or lactating.
  • The patient is known to be positive for infection with the human immunodeficiency virus.
  • The patient is receiving therapy with immune modulators such as cyclosporine or tacrolimus.
  • The patient has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.
  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: NCT00503685

Locations
United States, California
ImClone Investigational Site
Los Angeles, California, United States, 90095
United States, Connecticut
ImClone Investigational Site
New Haven, Connecticut, United States, 06520
United States, New York
ImClone Investigational Site
Buffalo, New York, United States, 14263
ImClone Investigational Site
New York, New York, United States, 10021
Sponsors and Collaborators
ImClone LLC
Investigators
Study Chair: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT00503685     History of Changes
Other Study ID Numbers: 13936, CP02-0657, CP13-0605, I5A-IE-JAEL
Study First Received: July 17, 2007
Last Updated: October 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Metastatic Colorectal Cancer with Disease Progression
Failed prior to Anti-EGFr Therapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Disease Progression
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Disease Attributes
Pathologic Processes
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014