Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
Condition: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: irinotecan hydrochloride; leucovorin calcium; fluorouracil; cetuximab; bevacizumab
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Cetuximab; Fluorouracil; Irinotecan; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying giving irinotecan and cetuximab together with
      bevacizumab to see how well it works compared with giving irinotecan and cetuximab alone in
      treating patients with metastatic colorectal cancer that progressed during first-line
      therapy. Drugs used in chemotherapy, such as irinotecan, 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 bevacizumab, 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. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether
      irinotecan and cetuximab are more effective with or without bevacizumab in treating
      metastatic colorectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have metastatic colorectal cancer that has been histologically or
             cytologically confirmed; confirmation may be from either the primary tumor or a
             metastasis; patients must have wild type KRAS

          -  Patients must be registered within 28 days of documented disease progression on first
             line chemotherapy with bevacizumab plus either FOLFOX, OPTIMOX, or XELOX; this
             progression must have occurred within 90 days after the last dose of bevacizumab;
             patients who discontinued oxaliplatin, continued with 5-FU/LV or capecitabine and
             bevacizumab and then had subsequent progression while on fluoropyrimidine and
             bevacizumab are eligible; patients who discontinued bevacizumab due to adverse events
             in the first-line setting are not eligible

          -  Measurable or nonmeasurable disease

          -  At least 14 days must have elapsed since the last dose of first line chemotherapy and
             bevacizumab

          -  Patients must not have received prior treatment with irinotecan (either as adjuvant or
             metastatic treatment)

          -  Patients must have no history of prior treatment with cetuximab or other agents
             targeting VEGF or EGFR (except for bevacizumab)

          -  Prior radiotherapy is allowed, provided at least 28 days have elapsed since the last
             treatment; all adverse events related to radiation therapy must be resolved

          -  Prior surgery is allowed, provided at least 28 days have elapsed since any major
             surgery and patient has recovered from all effects

          -  Zubrod performance status 0-2

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< 1.5 times upper limit of normal (ULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase
             (SGPT) =< 2.5 x IULN; if there are known liver metastases, SGOT or SGPT must be =< 5 x
             IULN; these results must be obtained within 28 days prior to registration

          -  Serum creatinine =< IULN or measured or estimated creatinine clearance >= 60 mL/min

          -  Patients must not have a history or known presence of brain metastasis

          -  Patients may be on full dose anticoagulation with warfarin provided that the patient
             has an acceptable International Normalized Ratio (INR) (between 2 and 3), obtained
             within 28 days prior to registration

          -  No clinically relevant bleeding diathesis or coagulopathy

          -  Patients must not have experienced nephrotic range proteinuria from prior bevacizumab
             therapy; urine protein must be screened by urine analysis for Urine Protein Creatinine
             (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level
             must be < 1,000 mg for patient enrollment; urine protein and creatinine used in
             calculating the UPC ratio must be obtained within 28 days prior to registration

          -  No uncontrolled high blood pressure (BP) (i.e., systolic BP > 150 mm Hg and diastolic
             BP > 90 mm Hg)

          -  No cardiovascular event within the past 6 months, including any of the following:

               -  Arterial thrombosis

               -  Unstable angina

               -  Myocardial infarction

               -  Cerebrovascular accident

          -  Patients must not have New York Heart Association (NYHA) >= Grade 2 congestive heart
             failure

          -  Patients must not have unstable symptomatic arrhythmia requiring medication; (patients
             with chronic, controlled arrhythmias such as atrial fibrillation or paroxysmal
             supraventricular tachycardia [PSVT] are eligible)

          -  No clinically significant peripheral vascular disease

          -  No serious or nonhealing active wound, ulcer, or bone fracture

          -  No history of gastrointestinal (GI) perforation while on prior bevacizumab

          -  No significant bleeding episodes (e.g., hemoptysis or upper or lower GI bleeding)
             within the past 6 months unless the source of bleeding has been resected

          -  No known hypersensitivity to bevacizumab or known potential hypersensitivity to
             cetuximab

          -  No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or
             any other type of anticancer treatment

          -  Due to the possibility of harm to a fetus or nursing infant from this treatment
             regimen, patients must not be pregnant or nursing; women and men of reproductive
             potential must have agreed to use an effective contraceptive method

          -  No other malignancy within the past 5 years except for adequately treated basal or
             squamous cell skin cancer or cervical cancer in situ

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines

          -  At the time of patient registration, the treating institution's name and
             identification (ID) number must be provided to the Data Operations Center in Seattle
             in order to ensure that the current (within 365 days) date of institutional review
             board approval for this study has been entered into the data base