Radiolabeled Monoclonal Antibody, Paclitaxel, and Interferon Alfa in Treating Patients With Recurrent Ovarian Cancer

OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of intraperitoneal paclitaxel and topotecan when administered as a radiosensitizer prior to intraperitoneal lutetium Lu 177 monoclonal antibody CC49 (177Lu-CC49) following subcutaneous interferon alfa-2b (IFN-A) in patients with persistent or recurrent ovarian cancer.

II. Determine the toxicity associated with intraperitoneal paclitaxel and topotecan in these patients.

III. Examine the conjugate stability, pharmacokinetics, and biodistribution of 177Lu-CC49 given 48 hours after intraperitoneal paclitaxel.

IV. Determine the effects of IFN-A and intraperitoneal paclitaxel on 177Lu-CC49 tumor localization and dosimetry estimates compared to a prior trial with 177Lu-CC49 alone.

V. Determine the MTD of yttrium Y 90 monoclonal antibody CC49 (90Y-CC49) when administered with IFN-A and the dose of paclitaxel used at the MTD level of IFN-A, paclitaxel, and 177Lu-CC49.

VI. Monitor any antitumor effects of this treatment in these patients.

OUTLINE: This is a dose escalation study of paclitaxel, topotecan, lutetium LU 177 monoclonal antibody CC-49 (177Lu-CC49), and yttrium Y 90 monoclonal antibody CC49 (90Y-CC49).

Patients receive interferon alfa subcutaneously on days 1, 3, 5, and 7; paclitaxel intraperitoneally (IP) on day 4 or topotecan IP on day 6; and 177Lu-CC49 IP on day 6. Treatment continues every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of paclitaxel and decreasing doses of 177Lu-CC49 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 5 patients experience dose limiting toxicity. Once the MTD of paclitaxel is determined, the dose of 177Lu-CC49 is escalated. Once the MTD of 177Lu-CC49 is determined, 90Y-CC49 is substituted. The MTD of 90Y-CC49 is then determined when administered with paclitaxel. Topotecan is then substituted for paclitaxel (administered with the MTD of 177Lu-CC49 and interferon alfa only) and escalated until the MTD is determined. Patients are followed at 6 weeks and then every 3 months for 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the ovary or papillary serous carcinoma of extraovarian origin
• Recurrent or persistent following standard surgery and 1 or 2 chemotherapy regimens (with or without paclitaxel), i.e.: persistent disease or progression after chemotherapy with nodules less than the equivalent of 5 x 5 x 5 cm Recurrent carcinoma (after primary or secondary chemotherapy) detected clinically either by exam or rising CA 125 and with radiographic evidence of disease no greater than the equivalent of 5 x 5 x 5 cm nodules
• Residual disease less than 5 x 5 x 5 cm following reassessment laparotomy
• Microscopic residual disease on reassessment laparotomy after chemotherapy
• Tumor TAG-72 positive by immunoperoxidase staining of original or current tumor blocks
• At least 85% free flow of fluid in peritoneal cavity demonstrated by technetium-99m scan or other imaging within 2 weeks prior to treatment
• No evidence of disease outside the peritoneal cavity other than retroperitoneal lymphadenopathy
• No massive ascites

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: ECOG 0-2
• WBC at least 3,500/mm3
• Platelet count at least 125,000/mm3
• Hemoglobin greater than 9 g/dL
• No nucleated RBC or significant teardrop RBC morphology
• Bilirubin less than 1.5 mg/dL
• AST/ALT less than 4 times normal
• Creatinine less than 2.0 mg/dL
• HIV negative
• Hepatitis B surface antigen negative
• No hypersensitivity to paclitaxel, polyoxethylated castor oil, or topotecan
• No other malignancy in past 5 years except basal cell skin carcinoma
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior biologic therapy and recovered
• No prior monoclonal antibody therapy
• No concurrent immunotherapy
• No prior bone marrow or stem cell transplantation
• At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) and recovered
• No concurrent chemotherapy
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to the abdominal cavity
• No concurrent radiotherapy
• At least 3 weeks since prior major surgery and recovered
• No prior intraperitoneal therapy