monoclonal antibody therapy in treating patients with relapsed or refractory small cell lung cancer

Conditions: Lung 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 trial to study the effectiveness of monoclonal antibody therapy in treating patients who have relapsed or refractory small cell lung cancer.

objectives: * determine the dose limiting toxicity and maximum tolerated dose of yttrium y 90 anti-cea monoclonal antibody mn-14 in patients with relapsed or refractory small cell lung cancer. * determine the dosimetric and pharmacokinetic properties of this treatment regimen in the blood, normal organs, and tumors of these patients. * determine the stability and complexation with circulating carcinoembryonic antigen of this radioantibody in the plasma of these patients. * determine the antibody response of these patients treated with this regimen. * determine the antitumor effects of this treatment regimen in these patients. outline: this is a dose escalation study of yttrium y 90 anti-cea monoclonal antibody mn-14 (90y-hmn-14). patients are stratified according to prior radiotherapy (yes vs no). patients undergo pretherapy imaging with indium in 111 anti-cea monoclonal antibody mn-14 iv over 30-40 minutes on day -7 or -6 followed by external scintigraphy on days -7 or -6 to 0. patients who show positive localization of at least one documented tumor site receive 90y-hmn-14 iv over 30-40 minutes on day 0. cohorts of 3-6 patients receive escalating doses of 90y-hmn-14 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose limiting toxicity. patients are followed at 2, 4, 8, and 12 weeks; every 3 months for 2 years; and then every 6 months for 3 years. projected accrual: a total of 15-30 patients will be accrued for this study within 10-14 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed small cell lung cancer (sclc) * must have received at least one prior course of standard chemotherapy and, if indicated, up to 6,900 cgy of thoracic radiotherapy * patients who received prior radiotherapy must show evidence of progressive disease * patients who received no prior radiotherapy to the primary tumor must show evidence of stable or progressive disease * measurable disease * must have evidence of carcinoembryonic antigen (cea) production or expression documented by one of the following: * serum cea at least 10 ng/ml * positive immunohistology of either the primary tumor or a metastasis with cea specific monoclonal antibody * must have unilateral bone marrow biopsy with less than 25% tumor involvement * no known, active brain metastases patient characteristics: age: * 18 and over performance status: * karnofsky 70-100% * ecog 0-2 life expectancy: * at least 3 months hematopoietic: * wbc at least 3,000/mm\^3 * granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 2 mg/dl * ast no greater than 2 times upper limit of normal (uln) * no hepatitis b or c * no other serious liver abnormality renal: * creatinine no greater than 1.5 times uln * no urinary incontinence cardiovascular: * ejection fraction at least 50% pulmonary: * fev_1 and fvc at least 60% * dlco at least 50% predicted other: * no severe anorexia, nausea, or vomiting * no other significant medical problems * no prisoners * no reactivity to humanized mn-14 (in patients with prior exposure to chimeric or humanized antibody) * hiv negative * no active hiv-related disease * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for at least 3 months following study participation prior concurrent therapy: biologic therapy: * see chemotherapy * no concurrent growth factors (e.g., filgrastim \[g-csf\]) chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy * no prior high dose chemotherapy with stem cell transplantation endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy * prior radiotherapy to less than 30% of red marrow (including standard chest x-ray for limited stage sclc) allowed surgery: * at least 4 weeks since prior major surgery

Keywords: recurrent small cell lung cancer