radiolabeled monoclonal antibody plus peripheral stem cell transplantation in treating patients with refractory or recurrent ovarian epithelial cancer

Conditions: Ovarian Cancer

Summary: rationale: radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. peripheral stem cell transplantation may be able to replace immune cells that were destroyed by therapy used to kill tumor cells. purpose: phase i/ii trial to study the effectiveness of radiolabeled monoclonal antibody plus peripheral stem cell transplantation in treating patients who have refractory or recurrent ovarian epithelial cancer.

objectives: i. determine the normal organ and tumor dosimetry with yttrium y 90 monoclonal antibody mn-14 using indium in 111 monoclonal antibody mn-14 as pretherapy in patients with advanced ovarian epithelial cancer. ii. evaluate the extent and duration of antitumor response in these patients on this regimen. outline: this is a dose escalation study of yttrium y 90 monoclonal antibody mn-14 (90y hmn-14). patients receive filgrastim (g-csf) subcutaneously (sq) on days -17 to -13, followed by leukapheresis on days -14 to -12. if an adequate number of cd34+ cells are not harvested, bone marrow is also collected. patients receive pretherapy targeting consisting of indium in 111 monoclonal antibody mn-14 over 30 minutes on day -7. at least 1 confirmed tumor site must be targeted. patients receive 90y hmn-14 iv over 30-45 minutes on day 0. pbsc is reinfused within 7 to 14 days after 90 hmn-14 administration. patients receive g-csf sq or iv until blood counts recover. 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 either the dose at which no more than 1 of 6 patients experiences dose limiting toxicity or the threshold radiation doses to lungs, kidney, and liver are reached. patients are followed weekly for 1 month, every 2 weeks for 2 months, monthly for 3 months, every 3 months for 2 years, and then every 6 months for 5 years. projected accrual: approximately 48-51 patients will be accrued for this study within 5 years.

Eligibility criteria:
disease characteristics: histologically or cytologically refractory or recurrent ovarian epithelial cancer resistant to platinum or taxane containing chemotherapy within past 6 months autologous peripheral blood stem cells (pbsc) or bone marrow available at least 1 measurable site confirmed by ct targeted pretherapy indium in 111 monoclonal antibody mn-14 imaging no bone marrow involvement patient characteristics: age: 18 to 80 performance status: karnofsky 70-100% ecog 0-2 life expectancy: at least 3 months hematopoietic: wbc at least 3,000/mm3 granulocyte count at least 1,500/mm3 platelet count at least 100,000/mm3 hepatic: bilirubin no greater than 2.0 mg/dl sgot less than 2.0 times upper limit of normal (uln) renal: creatinine less than 1.5 times uln creatinine clearance at least 50 ml/min cardiovascular: lvef at least 50% by muga pulmonary: fvc, fev1, and dlco at least 70% of predicted other: not pregnant fertile patients must use effective contraception during and for 3 months after study no aids-related illness no concurrent significant medical complications that would preclude compliance no severe anorexia, nausea, or vomiting no history of allergy or antibodies to 90y hmn-14 prior concurrent therapy: biologic therapy: no prior imaging studies with murine monoclonal antibodies showing reactivity with yttrium y 90 monoclonal antibody mn-14 (90y hmn-14) chemotherapy: at least 4 weeks since prior chemotherapy and recovered endocrine therapy: not specified radiotherapy: at least 4 weeks since prior radiotherapy to index lesion and recovered no prior radiotherapy to greater than 25% of red marrow no prior radiotherapy to maximum tolerated levels for any critical organ (e.g., lung, liver, or kidney) surgery: at least 4 weeks since prior major surgery other: no concurrent antiretroviral medication

Keywords: recurrent ovarian epithelial cancer