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

• Status: Active, not recruiting
• Trial end date: 2022-07-06
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eastern Cooperative Oncology Group; Pam Cogliano
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bevacizumab; Camptothecin; Cetuximab; Irinotecan; Ramucirumab

Criteria

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