Irinotecan and Cediranib in Treating Patients With Metastatic Colorectal Cancer That Did Not Respond to Previous Oxaliplatin, Fluoropyrimidine, and Bevacizumab
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: cediranib maleate; irinotecan hydrochloride
Intervention MeSH terms: Irinotecan; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Summary:

      RATIONALE: 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.
      Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Giving irinotecan together with cediranib may kill more tumor cells.

      PURPOSE: This phase II clinical trial is studying how well giving irinotecan together with
      cediranib works in treating patients with metastatic colorectal cancer that did not respond
      to previous oxaliplatin, fluoropyrimidine, and bevacizumab.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically documented metastatic colorectal cancer

               -  The site of the primary lesion must be or have been confirmed endoscopically,
                  surgically, or radiologically to have been in the colon or rectum

               -  Patients with a history of histologically proven colorectal cancer treated by
                  surgical resection and who develop radiological or clinical evidence of
                  metastatic cancer do not require additional histological or cytological
                  confirmation of metastatic disease unless either of the following are true:

                    -  An interval of greater than five years has elapsed between the primary
                       surgery and the development of metastatic disease

                    -  The primary cancer was stage I

          -  Must have measurable disease, defined as in at least one dimension (longest dimension
             to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

               -  Lesions that are considered nonmeasurable include the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural/pericardial effusion

                    -  Lymphangitis cutis/pulmonis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  Must have received one and only one prior regimen for metastatic disease containing
             oxaliplatin, a fluoropyrimidine, and bevacizumab

               -  Patients who discontinue oxaliplatin due to toxicity are eligible provided they
                  progressed on the fluoropyrimidine component with or without bevacizumab

          -  No known brain metastases

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  ANC ≥ 1,500/μL

          -  Platelet count ≥ 100,000/μL

          -  Hemoglobin ≥ 8 g/dL

          -  Leukocytes ≥ 3,000/mm³

          -  Calculated creatinine clearance > 50 mL/min

          -  ALT/AST ≤ 2.5 times upper limit of normal (ULN)

          -  Urine protein < 1+ protein OR protein < 1g by 24-hour urine collection and urine
             protein:creatinine ratio < 1.0

          -  Total bilirubin normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  No known end-stage liver disease or active hepatitis

          -  No colonic or small bowel disorders (e.g., inflammatory bowel disease, Crohn's
             disease, ulcerative colitis) that predispose to diarrhea in which the symptoms are
             uncontrolled as indicated by baseline pattern of > 3 watery or soft stools daily in
             patients without a colostomy or ileostomy

               -  Patients with a colostomy or ileostomy may be entered at investigator discretion

          -  History of hypertension allowed provided it is well controlled (BP < 150/90 mm Hg) on
             a regimen of antihypertensive therapy

          -  No concurrent congestive heart failure (New York Heart Association class III or IV)

          -  No significant history of bleeding events or gastrointestinal (GI) perforation

               -  Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper
                  or lower GI bleeding) within 3 months prior to beginning treatment are not
                  eligible unless the source of bleeding has been surgically resected

               -  Patients with a history of GI perforation within 12 months prior to beginning
                  treatment are not eligible

          -  No arterial thrombotic events within 6 months before beginning treatment, including
             any of the following:

               -  Transient ischemic attack

               -  Cerebrovascular accident

               -  Unstable angina or angina requiring surgical or medical intervention within the
                  past 6 months

               -  Myocardial infarction

          -  No serious or nonhealing wound, ulcer, or bone fracture

          -  Patients with clinically significant peripheral artery disease (i.e., claudication on
             ambulating less than one block) or any other arterial thrombotic event within 6 months
             are also ineligible

          -  QTc interval ≤ 470 msec

          -  No personal or family history of long QT syndrome.

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Must have recovered from all acute toxicities of prior therapy for metastatic disease
             except peripheral neuropathy

          -  At least 6 weeks between the last dose of bevacizumab and the first dose of cediranib

          -  Prior pelvic irradiation is allowed (as long as the measurable lesion is outside the
             radiotherapy field)

          -  Completed any major surgery ≥ 4 weeks from start of treatment and completed any minor
             surgery ≥ 1 week prior to start of treatment

               -  Insertion of a vascular access device is not considered major or minor surgery
                  from the standpoint of protocol eligibility

               -  Patients must have fully recovered from the procedure and have a fully healed
                  incision

          -  Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both
             of the following criteria are met:

               -  The patient has an in-range INR (usually between 2 and 3) on a stable dose of
                  oral anticoagulant or is on a stable dose of low molecular weight heparin

               -  The patient has no active bleeding or pathological condition that carries a high
                  risk of bleeding (e.g., tumor involving major vessels or known varices)

          -  Patients receiving anti-platelet agents are eligible

          -  Patients who are on daily prophylactic aspirin or anticoagulation for atrial
             fibrillation are eligible

          -  The use of agents with strong proarrhythmic potential is not permitted during the
             study

          -  Patients who received treatment on CALGB-C80405 and whose treatment failed are
             eligible for this study