Hu3S193 in Treating Women With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

OBJECTIVES:

Primary

• To evaluate the efficacy of monoclonal antibody Hu3S193 in women with platinum-resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer, based on RECIST criteria (Response Evaluation Criteria in Solid Tumors).

Secondary

• To determine the safety of the study drug.
• To determine the drug pharmacokinetics when administered in multiple weekly injections.

Exploratory analysis

• Clinical Benefit (objective response rate + tumor stabilization).
• Progression Free Survival (PFS).
• Duration of Response.
• Overall Survival.
• 12-month survival rate.

OUTLINE: This is a multicenter study.

Patients receive monoclonal antibody Hu3S193 IV over 1 hour once weekly in weeks 1-8. Treatment repeats every 8 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

• Progressive disease
• Disease must express Lewis-Y antigen documented by immunohistochemistry in archived or fresh primary or metastatic tumor biopsies
• Measurable disease, including at least one measurable lesion, according to RECIST criteria or CA-125 (Cancer Antigen-125) > 2 times upper normal limit

• Pleural effusion, ascites, bone metastases, and lesions located in previously irradiated areas are not considered measurable
• Disease must be considered platinum-refractory or resistant, meeting any of the following criteria:

• Platinum-refractory defined as progression during the initial platinum-based chemotherapy regimen or failure to achieve a complete response (e.g., stable disease or partial response) with evidence of progressive disease (by physical examination, radiological exams, or CA-125) during the initial platinum-based chemotherapy
• Platinum-resistant defined as recurrence within six months of completion of the initial platinum-based regimen (primary platinum-resistance) or recurrence after six months of completion of the initial platinum-based regimen (still considered platinum-sensitive, but incurable by any approach, that will progress to a secondary platinum-resistance scenario) and failure to ≥ 1 re-induction with a platinum-based regimen (secondary platinum-resistance)
• No high tumor burden, as assessed by the investigator
• No rapidly progressing disease, as assessed by clinical evaluation
• No known CNS (Central Nervous System) involvement by tumor

PATIENT CHARACTERISTICS:

Inclusion criteria

• Karnofsky performance status > 70%
• Life expectancy ≥ 12 weeks
• ANC (absolute neutrophil count) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Serum bilirubin ≤ 2.0 mg/dL
• AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if with liver metastases)
• Creatinine ≤ 2.0 mg/dL
• Prothrombin time < 1.3 times control
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria

• NYHA (New York Heart Association) class III or IV heart disease
• Clinically significant arrhythmias by ECG
• Myocardial infarction within the past 6 months
• Any other serious illness, including any of the following:

• Severe ascites
• Severe active infections requiring antibiotics
• Bleeding disorders
• Chronic inflammatory bowel disease
• Diseases that might interfere with the collection of accurate results from this study
• Positive for human anti-human antibodies
• Prior history of tumor (excluding adequately treated nonmelanoma skin cancer or carcinoma in situ of the uterine cervix)
• Uncontrolled hypercalcemia (i.e., > 11.5 mg/dL)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from the toxic effects of any prior therapy
• No concurrent systemic steroids or immunosuppressant agents
• No more than 1 prior non-platinum-containing regimen for the treatment of platinum-resistant/refractory disease

• Patients who receive 2 or more different non-platinum-containing chemotherapy regimens for platinum-resistant/refractory disease are not eligible
• More than 4 weeks since prior and no other concurrent chemotherapy, radiotherapy, radiopharmaceuticals (e.g., ^32P), biological therapy, anti-estrogen therapy (including tamoxifen), immunotherapy, or surgery
• More than12 weeks since prior investigational agent
• No prior treatment with a murine or humanized antibody and/or antibody fragment