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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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified June 2012 by Pam Cogliano, Eastern Cooperative Oncology Group.
Recruitment status was:  Recruiting
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pam Cogliano, Eastern Cooperative Oncology Group Identifier:
First received: March 2, 2010
Last updated: September 19, 2014
Last verified: June 2012

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.

Condition Intervention Phase
Colorectal Cancer Biological: cetuximab Biological: ramucirumab Drug: irinotecan hydrochloride Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Pam Cogliano, Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Progression-free survival

Secondary Outcome Measures:
  • Response rate (complete response, partial response, stable disease)
  • Toxicity
  • Overall survival

Estimated Enrollment: 147
Study Start Date: November 2010
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1.
Biological: cetuximab
Given IV
Drug: irinotecan hydrochloride
Given IV
Experimental: Arm II
Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm I.
Biological: cetuximab
Given IV
Biological: ramucirumab
Given IV
Drug: irinotecan hydrochloride
Given IV

Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  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 identifier: NCT01079780

  Show 255 Study Locations
Sponsors and Collaborators
Pam Cogliano
National Cancer Institute (NCI)
Principal Investigator: Howard S. Hochster, MD New York University School of Medicine
  More Information

Responsible Party: Pam Cogliano, Protocol Development Manager, Eastern Cooperative Oncology Group Identifier: NCT01079780     History of Changes
Other Study ID Numbers: CDR0000666736
Study First Received: March 2, 2010
Last Updated: September 19, 2014

Keywords provided by Pam Cogliano, Eastern Cooperative Oncology Group:
mucinous adenocarcinoma of the colon
recurrent colon cancer
signet ring adenocarcinoma of the colon
stage III colon cancer
stage IV colon cancer
mucinous adenocarcinoma of the rectum
recurrent rectal cancer
signet ring adenocarcinoma of the rectum
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on August 18, 2017