Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of People With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab (FC-4)

This study has been completed.
Sponsor:
Collaborator:
NSABP Foundation Inc
Information provided by (Responsible Party):
ImClone LLC
ClinicalTrials.gov Identifier:
NCT00845039
First received: February 10, 2009
Last updated: February 2, 2012
Last verified: July 2011
  Purpose

The purpose of this study is to determine the value of adding IMC-A12 to irinotecan and cetuximab in patients with metastatic colorectal cancer.


Condition Intervention Phase
Colon Cancer
Rectal Cancer
Biological: Cetuximab
Drug: Irinotecan
Biological: IMC-A12 (cixutumumab)
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 II Clinical Trial Investigating Irinotecan Plus Cetuximab With or Without Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody (IMC-A12) for the Treatment of Patients With Metastatic K-Ras Wild Type Carcinoma of the Colon or Rectum That Has Progressed on Oxaliplatin and Bevacizumab Given as First-Line Therapy

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR) (Complete Response plus Partial Response) [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) over entire duration [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Resection Rate, the number of patients who had a complete resection/ablation of metastases with no evidence of disease remaining [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Toxicity of the irinotecan + cetuximab + IMC-A12 regimen [ Time Frame: Approximately 18 months ] [ Designated as safety issue: Yes ]
    Number of patients experiencing grade 4 or 5 toxicities will be calculated among the first 12 randomized patients who receive at least 2 cycles of therapy or who have therapy discontinued secondary to an adverse event

  • Post-treatment serum levels of IMC-A12 in patients receiving IMC-A12 [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Change in Behavioral and Health Outcomes [BAHO] Quality of Life Questionnaire [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
    Change from baseline in the patient reported outcomes measured after 3rd cycle of study treatment and end of study therapy

  • Serum Anti-IMC-A12 Antibody Assessment [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: May 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cetuximab + Irinotecan
Patients in Treatment Group 1 will receive intravenous infusions of Cetuximab 500 mg/m2 and Irinotecan 180 mg/m2.
Biological: Cetuximab
Cetuximab 500 mg/m2 every 14 days until disease progression or patient intolerance
Other Name: Erbitux
Drug: Irinotecan
180 mg/m2 every 14 days until disease progression or patient intolerance
Other Name: Camptosar
Experimental: Cetuximab + IMC-A12 + Irinotecan
Patients in Treatment Group 2 will receive intravenous infusions of Cetuximab 500 mg/m2, IMC-A12 10mg/kg and Irinotecan 180 mg/m2.
Biological: Cetuximab
Cetuximab 500 mg/m2 every 14 days until disease progression or patient intolerance
Other Name: Erbitux
Drug: Irinotecan
180 mg/m2 every 14 days until disease progression or patient intolerance
Other Name: Camptosar
Biological: IMC-A12 (cixutumumab)
IMC-A12 10mg/kg every 14 days until disease progression or patient intolerance
Other Name: Cixutumumab

Detailed Description:

The purpose of this study is to determine the value of adding IMC-A12 to irinotecan + cetuximab in improving PFS at 18 weeks from the date of randomization for patients with metastatic K-RAS wild-type CRC that has progressed on an oxaliplatin/bevacizumab-containing regimen.

  Eligibility

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

Inclusion Criteria:

  • Must consent to be in the study and must have signed and dated IRB-approved consent forms conforming to federal and institutional guidelines for the pre-entry tumor sample submission for central K-RAS testing and for the study treatment
  • Must have an ECOG performance status of 0, 1, or 2
  • Must have metastatic CRC
  • The CRC tumor or metastatic tumor must be K-RAS wild-type as determined by central testing
  • Must be documented disease progression during first-line therapy containing both oxaliplatin and bevacizumab
  • Most recent treatment regimen must have ended ≥ 21 days prior to randomization, and clinically significant side effects associated with previous therapy must have resolved to ≤ grade 1 with the exception of neuropathy which must have resolved to ≤ grade 2
  • Imaging of the chest, abdomen and pelvis with CT scan or MRI must be performed within 3 weeks prior to randomization
  • Must have measurable disease, defined as at least one lesion outside a previous RT field that can be accurately measured in at least one dimension as ≥ 20mm with conventional techniques or as ≥ 10mm with 5mm cuts using a spiral CT scan
  • Evidence of adequate bone marrow function: ANC ≥ 1200/mm3, hemoglobin ≥ 9g/dL, platelets ≥ 100,000/mm3
  • Evidence of adequate hepatic function. If no liver metastases: AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN for the lab. In the presence of liver metastases: AST ≤ 5.0 x ULN, total bilirubin ≤ 1.5 x ULN for the lab
  • Serum creatinine must be ≤ 1.5 x ULN for the lab
  • Must have a fasting blood glucose < 126mg/dL. Fasting is defined as no caloric intake for at least 8 hours

Exclusion Criteria:

  • Life expectancy less than 12 weeks
  • Diagnosis of anal or small bowel carcinoma
  • Tumor that is considered by the surgeon to be amenable to complete resection
  • Previous radiation therapy to > 25% of bone marrow
  • Radiation therapy to sites of measurable disease chosen as target lesions
  • Radiological evidence and/or clinical signs or symptoms of CNS metastases
  • Any of the following conditions and events: uncontrolled hypertension, defined as systolic BP > 150mmHg or diastolic BP > 100 with or without antihypertensive medication (patients with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; NYHA Class III or IV cardiac disease; myocardial infarction within 6 months before randomization; symptomatic arrhythmia; CNS cerebrovascular ischemia (TIA or stroke) within 6 months before randomization
  • Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 12 months prior to randomization. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
  • Serious or non-healing wound, skin ulcers, or bone fracture
  • Any significant bleeding unless the source of bleeding has been resected
  • History of bleeding diathesis or coagulopathy (patients on stable anticoagulant therapy are eligible)
  • Any evidence of active infection
  • Active inflammatory bowel disease
  • Grade 3 or 4 diabetes mellitus as defined by NCI's CTCAE v 3.0 pancreatic endocrine: glucose intolerance (patients with diabetes controlled with diet and/or oral medications are eligible)
  • Symptomatic interstitial pneumonitis or definitive evidence of interstitial pneumonitis described on CT scan or chest x-ray in asymptomatic patients
  • Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study
  • Previous hypersensitivity reaction to monoclonal antibodies
  • Previous treatment with irinotecan, cetuximab, or any agent specifically targeting IGF receptors
  • Treatment with an investigational drug within 30 days prior to randomization
  • Pregnancy or lactation at the time of patient entry
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
  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: NCT00845039

Locations
United States, California
ImClone Investigational Site
Vallejo, California, United States, 94589
United States, North Carolina
ImClone Investigational Site
Greenville, North Carolina, United States, 27834
United States, Pennsylvania
ImClone Investigational Site
Scranton, Pennsylvania, United States, 18510
Sponsors and Collaborators
ImClone LLC
NSABP Foundation Inc
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT00845039     History of Changes
Other Study ID Numbers: 13928, CP13-0708, I5A-IE-JAED, NSABP FC-4
Study First Received: February 10, 2009
Last Updated: February 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Tumors
Antibodies, Monoclonal
Colorectal Neoplasms
Metastatic K-RAS Wild-Type Carcinoma of the Colon or Rectum

Additional relevant MeSH terms:
Bevacizumab
Cetuximab
Irinotecan
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014