Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: cetuximab; ramucirumab; irinotecan hydrochloride
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Irinotecan; Cetuximab; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 136.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Measurable disease

          -  Histologically confirmed adenocarcinoma of the colon or rectum

          -  K-ras wild type based on either primary or metastatic tumor

          -  Must have received prior first-line therapy comprising oxaliplatin-based
             fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal
             cancer

          -  Registration within 42 days since confirmed disease progression

          -  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])

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study therapy

          -  At least 28 days and no more than 90 days since prior bevacizumab

          -  Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed

        Exclusion Criteria:

          -  Brain or CNS metastases

          -  Pregnant or nursing

          -  Prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus
             bevacizumab for colorectal cancer

          -  Clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes within
             the past 3 months

          -  Active infection

          -  Symptomatic congestive heart failure

          -  Unstable angina pectoris

          -  Symptomatic or poorly controlled cardiac arrhythmia

          -  Uncontrolled thrombotic or hemorrhagic disorder

          -  Uncontrolled or poorly controlled hypertension despite standard medical management
             (e.g., consistently systolic BP > 160 mm Hg and diastolic BP > 90 mm Hg)

          -  Acute arterial thrombotic events within the past 6 months, including cerebrovascular
             accident, transient ischemic attack, myocardial infarction, or unstable angina

          -  Other cancer requiring therapy within the past 3 years except in situ carcinoma or
             nonmelanoma skin cancer

          -  Acute or subacute intestinal obstruction

          -  History of inflammatory bowel disease requiring pharmacological and/or surgical
             intervention within the past 12 months

          -  Known allergy to any of the treatment components

          -  Major surgery within the past 28 days

          -  Subcutaneous venous access device placement within the past 7 days