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Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy

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ClinicalTrials.gov Identifier: NCT01079780
Recruitment Status : Active, not recruiting
First Posted : March 3, 2010
Last Update Posted : July 19, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pam Cogliano, Eastern Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE March 2, 2010
First Posted Date  ICMJE March 3, 2010
Last Update Posted Date July 19, 2019
Actual Study Start Date  ICMJE October 8, 2010
Estimated Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
Progression-free survival
Original Primary Outcome Measures  ICMJE
 (submitted: March 2, 2010)
  • Progression-free survival
  • Response rate (complete response, partial response, stable disease)
  • Toxicity
Change History Complete list of historical versions of study NCT01079780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
  • Response rate (complete response, partial response, stable disease)
  • Toxicity
  • Overall survival
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy
Official Title  ICMJE A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab (IMC-1121B), in Advanced, K-ras Wild-Type Colorectal Cancer Following Progression on Bevacizumab-Containing Chemotherapy
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy.

Detailed Description

OBJECTIVES:

  • To evaluate the progression-free survival of patients with advanced K-ras wild-type colorectal cancer, following progression on bevacizumab-contained chemotherapy, treated with irinotecan hydrochloride and cetuximab with versus without ramucirumab as second-line therapy.
  • To evaluate the response rate in patients treated with these regimens.
  • To evaluate the grade 3-4 toxicity rates of these regimens in these patients.
  • To evaluate the overall suvival of patients treated with these regimens.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), discontinuation of oxaliplatin before disease progression (yes vs no), and time to disease progression since last treatment (≤ 6 months vs > 6 months). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1.
  • Arm II: Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm I.

In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up periodically for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: cetuximab
    Given IV
  • Biological: ramucirumab
    Given IV
  • Drug: irinotecan hydrochloride
    Given IV
Study Arms  ICMJE
  • Experimental: Arm I
    Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1.
    Interventions:
    • Biological: cetuximab
    • Drug: irinotecan hydrochloride
  • Experimental: Arm II
    Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm I.
    Interventions:
    • Biological: cetuximab
    • Biological: ramucirumab
    • Drug: irinotecan hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 12, 2017)
135
Original Estimated Enrollment  ICMJE
 (submitted: March 2, 2010)
147
Estimated Study Completion Date  ICMJE July 1, 2023
Estimated Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the colon or rectum, including:

    • Advanced disease
    • Histologic variants of adenocarcinoma allowed
    • K-ras wild type based on either primary or metastatic tumor

      • No mutated type
  • Measurable disease
  • Must have received prior first-line therapy comprising oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer
  • No more than 42 days since confirmed disease progression
  • No brain or CNS metastases

PATIENT CHARACTERISTICS:

  • Performance status 0-1
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 75,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min
  • Urine protein ≤ 1+ on dipstick or routine urinalysis (if ≥ 2+, a 24-hour urine collection must demonstrate < 1,000 mg of protein)
  • Total bilirubin ≤ 2.0 mg/dL
  • AST and ALT ≤ 3.0 times ULN (5.0 times ULN for patients with liver metastases)
  • INR ≤ 1.6 (≤ 3.0 for patients on warfarin and no active bleeding [i.e., no bleeding within the past 14 days])
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • No clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes within the past 3 months
  • None of the following:

    • Active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Symptomatic or poorly controlled cardiac arrhythmia
    • Uncontrolled thrombotic or hemorrhagic disorder
  • No uncontrolled or poorly controlled hypertension despite standard medical management (e.g., consistently systolic BP > 160 mm Hg and diastolic BP > 90 mm Hg)
  • No acute arterial thrombotic events within the past 6 months, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina
  • No other cancer requiring therapy within the past 3 years except in situ carcinoma or nonmelanoma skin cancer
  • No acute or subacute intestinal obstruction
  • No history of inflammatory bowel disease requiring pharmacological and/or surgical intervention within the past 12 months
  • No known allergy to any of the treatment components

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 28 days and no more than 90 days since prior bevacizumab
  • No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for colorectal cancer
  • No major surgery within the past 28 days
  • No subcutaneous venous access device placement within the past 7 days
  • Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01079780
Other Study ID Numbers  ICMJE CDR0000666736
ECOG-E7208
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pam Cogliano, Eastern Cooperative Oncology Group
Study Sponsor  ICMJE Pam Cogliano
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Howard S. Hochster, MD NYU Langone Health
PRS Account Eastern Cooperative Oncology Group
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP