monoclonal antibody therapy in treating patients with advanced colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. purpose: phase i/ii trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer that has not responded to irinotecan.

objectives: * determine the recommended phase ii dose of monoclonal antibody anti-anb3 integrin in patients with irinotecan-refractory advanced colorectal cancer. * determine the safety and tolerance of this drug in these patients. * determine any antitumor activity of this drug in these patients. * determine the objective response rate, response duration, and time to progression in patients treated with this drug. * determine the pharmacokinetics of this drug in these patients. outline: this is a dose-escalation study. patients receive monoclonal antibody anti-anb3 integrin iv over 30 minutes once weekly on weeks 1-52 in the absence of disease progression or unacceptable toxicity. patients with responding disease may continue therapy. cohort of 4-6 patients receive escalating doses of monoclonal antibody anti-anb3 integrin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 4 or 6 patients experience dose-limiting toxicity. once the mtd is determined, additional patients are treated at that dose in the phase ii portion of the study. patients are followed every 3 months for 2 years. projected accrual: a total of 4-24 patients will be accrued for phase i of this study and a total of 40 patients will be accrued for phase ii of this study.

Eligibility criteria:
disease characteristics: * histologically confirmed advanced colorectal cancer * disease progression while receiving an irinotecan-containing regimen for metastatic colorectal cancer or * disease recurrence within 6 months after completing an irinotecan-containing regimen in the adjuvant setting * at least 1 measurable lesion (for phase ii only) * at least 20 mm by x-ray, ct scan, mri, or photograph * recurrent disease after surgery or radiotherapy is considered measurable if it has been at least 4 weeks since treatment and measurable disease is outside the port of prior radiotherapy or there is evidence of disease progression within the port of prior radiotherapy * the following are not considered measurable: * pleural effusion * ascites * osteoblastic lesion or evidence of disease on bone scan alone * progressive irradiated lesions alone * bone marrow involvement * brain metastases * malignant hepatomegaly by physical exam alone * chemical markers (e.g., carcinoembryonic antigen) * no known brain metastases or primary brain tumors * no symptomatic pleural effusion or ascites requiring paracentesis * no clinical evidence of bowel obstruction patient characteristics: age: * 18 and over performance status: * ecog 0-1 life expectancy: * not specified hematopoietic: * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin greater than 10.0 g/dl hepatic: * bilirubin no greater than 2.0 mg/dl * ast/alt no greater than 5 times upper limit of normal (uln) * pt/ptt less than uln or * inr less than 1.12 * no hepatitis virus infection renal: * creatinine no greater than 1.5 mg/dl or * creatinine clearance greater than 50 ml/min cardiovascular: * no prior myocardial infarction * no angina * no uncontrolled hypertension (systolic blood pressure greater than 150 mm hg) * no prior cerebrovascular accident or transient ischemic attack pulmonary: * no respiratory insufficiency requiring oxygen treatment * no lymphangitic involvement of lungs other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception for 30 days before, during, and for 30 days after study * thyroxine and thyroid-stimulating hormone normal * no hematemesis, melena, hematochezia, or gross hematuria * no prior significant adverse reaction to a humanized monoclonal antibody * no known hiv infection * no active infection requiring systemic anti-infective therapy * no other medical or psychological condition or behavior, including substance dependence or abuse, that would preclude study * no other malignancy within the past 5 years except basal cell skin cancer or completely excised carcinoma in situ of the cervix prior concurrent therapy: biologic therapy: * prior immunotherapy with approved agents allowed * no prior monoclonal antibody anti-anb3 integrin or its precursor (medi-523) * no other concurrent immunotherapy chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy * no concurrent palliative chemotherapy endocrine therapy: * no concurrent hormonal therapy radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy surgery: * see disease characteristics * at least 4 weeks since prior surgery and surgical wounds must have healed other: * recovered from all prior therapy * at least 4 weeks since prior investigational agents

Keywords: recurrent colon cancer recurrent rectal cancer