Ixabepilone in Treating Patients With Relapsed and/or Refractory Stage III or Stage IV Ovarian Epithelial or Primary Peritoneal Cancer

Phase II Study Of Epothilone B Analogue BMS-247550 In Relapse And/Or Refractory Stage III Or IV Ovarian Epithelial Cancer, Following Front-Line Treatment With Platinum Plus Taxane-Based Chemotherapy

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of ixabepilone in treating patients who have relapsed and/or refractory stage III or stage IV ovarian epithelial cancer or primary peritoneal cancer.

OBJECTIVES:

Primary

• Determine the antitumor activity of ixabepilone, in terms of clinical response and progression-free survival, in patients with relapsed and/or refractory stage III or IV ovarian epithelial or primary peritoneal cancer.
• Determine the nature and degree of toxicity of this drug in these patients.

Secondary

• Correlate pre-ixabepilone survivin mRNA and protein levels in patient-derived ovarian cancer cells with quality of response (i.e., at least partial response vs no response).
• Correlate CYP3A4 (3A4*1B), 3A5 (3A5*1), and 3A7 (ER6 p variation) allelic polymorphisms with parent drug kinetic parameters, toxicity, and efficacy of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive ixabepilone IV over 1 hour once weekly on weeks 1-3. Treatment repeats every 4 weeks for a total of 3 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage III or IV ovarian epithelial cancer or primary peritoneal carcinoma

  • Recurrent or refractory disease

    • Previously treated with 1, and only 1, prior chemotherapy regimen containing carboplatin, cisplatin, or another organoplatinum compound and paclitaxel or docetaxel
    • Initial treatment may include high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment

• Bidimensionally measurable disease by physical exam, CT scan, or MRI

  • Ascites and pleural effusions are not measurable disease
  • No prior irradiation to indicator lesions

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No prior bleeding disorder or unexplained bleeding

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• No active infection requiring antibiotics
• No grade 2 or greater neuropathy (sensory and motor)
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No prior recurrent grade 2 or greater hypersensitivity reactions to Cremophor EL, docetaxel, or paclitaxel
• No other medical condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior biologic or immunologic therapy for ovarian epithelial or primary peritoneal carcinoma

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered
• No prior ixabepilone
• No prior cytotoxic chemotherapy (including retreatment with initial chemotherapy regimens) for recurrent or persistent ovarian epithelial or primary peritoneal carcinoma

Endocrine therapy

• At least 1 week since prior hormonal therapy for ovarian epithelial or primary peritoneal carcinoma
• Concurrent hormonal replacement therapy allowed

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to a site of measurable disease used on study
• No prior radiotherapy to more than 25% of bone marrow

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• At least 3 weeks since other prior therapies for ovarian epithelial or primary peritoneal carcinoma
• No prior cancer treatment for other invasive malignancies that would preclude study participation
• No concurrent heparin or other anticoagulants
• No concurrent Hypericum perforatum (St. John's wort) or any product containing this compound