radiolabeled monoclonal antibody in treating patients with advanced colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. purpose: phase i trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients with advanced colorectal cancer.

objectives: i. define the toxicity and determine the maximum tolerated dose of iodine i 131 humanized monoclonal antibody a33 (131i-huab a33) in patients with advanced colorectal cancer. ii. describe pharmacokinetics and biodistribution of 131i-huab a33 by external imaging in these patients. iii. determine the effect of human antihuman antibody response on pharmacokinetics and targeting of 131i-huab a33 in this patient population. iv. determine whether the dose planning methodology used here can adequately and safely be applied to routine radioimmunotherapy planning. outline: patients receive iodine i 131 humanized monoclonal antibody a33 (131i-huab a33) by iv infusion over 20 minutes every 6-8 days for up to 8 weeks (depending on dosage). patients receive a minimum of 6 weeks of treatments. in the absence of disease progression or unacceptable toxicity, patients are retreated no sooner than 6 weeks after the previous course. cohorts of 3-6 patients receive escalating doses of 131i-huab a33 to determine the maximum tolerated dose (mtd). the mtd is defined as the highest dose at which no more than 2 of 6 patients experience dose limiting toxicity. patients are followed for 6 weeks after the last treatment. projected accrual: there will be 3-24 patients accrued into this study over 16 months.

Eligibility criteria:
disease characteristics: histologically confirmed advanced colorectal cancer must have unresectable (stage iv) disease or have failed or refused conventional chemotherapy measurable disease by conventional imaging methods liver involvement no greater than 50% no cns involvement not positive for human antimouse antibody titer patient characteristics: age: 18 and over performance status: karnofsky 80-100% life expectancy: at least 12 weeks hematopoietic: wbc at least 3,500/mm3 platelet count at least 150,000/mm3 prothrombin time less than 1.3 times control hepatic: bilirubin no greater than 1 mg/dl renal: creatinine no greater than 1.5 mg/dl cardiovascular: no significant cardiac disease (new york heart association class ii/iv heart disease) other: no serious infection requiring treatment with antibiotics no other serious illness not pregnant or nursing effective contraception required of all fertile patients prior concurrent therapy: biologic therapy: no prior mouse monoclonal antibody or antibody fragment, chimeric or humanized antibody, or constructs derived from antibodies at least 4 weeks since prior immunotherapy chemotherapy: no prior mitomycin/radiotherapy combination at least 4 weeks since prior chemotherapy endocrine therapy: no concurrent steroids or other antiinflammatory agents radiotherapy: no prior radiotherapy/mitomycin combination surgery: not specified

Keywords: stage iv colon cancer stage iv rectal cancer recurrent colon cancer recurrent rectal cancer