Fulvestrant in Treating Patients With Recurrent Ovarian Epithelial Cancer

Phase II Trial of Fulvestrant in Treatment of Recurrent Ovarian Carcinoma

RATIONALE: Estrogen can cause the growth of ovarian epithelial cancer cells. Hormone therapy using fulvestrant may fight ovarian cancer by blocking the use of estrogen by the tumor cells.

PURPOSE: This phase II trial is studying how well fulvestrant works in treating patients with recurrent ovarian epithelial cancer.

OBJECTIVES:

Primary

• To determine the 90-day clinical benefit (defined as the sum of complete responses, partial responses, and stable disease) in patients with recurrent ovarian epithelial cancer treated with single agent fulvestrant.

Secondary

• To establish the time to termination of treatment (due to all causes including progression and intolerance) for patients treated with this drug.
• To describe the toxicities observed in patients treated with this drug.
• To evaluate the quality of life of patients treated with this drug.
• To determine the effect that prolonged estrogen receptor antagonism has on markers of bone mineral turnover.

OUTLINE: Patients receive fulvestrant intramuscularly on days 1 and 15 of course 1 and then on day 1 of all subsequent courses. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients in continued response at the end of 1 year may continue treatment at the discretion of the treating physician.

Urinary N-telopeptide and serum skeletal-specific alkaline phosphatase are assessed at baseline and at 1, 3, and 6 months during study to determine the influence of estrogen blockade on bone mineral turnover.

Quality of life is assessed at baseline and every 3 months during treatment, and at the end of treatment using The Functional Assessment of Cancer Therapy - Ovarian (FACT-O) cancer questionnaire.

After completion of study treatment, patients are followed at approximately 30 days.

Inclusion Criteria:

• Histologically confirmed ovarian epithelial carcinoma

  • Recurrent or persistent disease

    • Must have received greater than or equal to (≥) 2 prior cytotoxic chemotherapy regimens, including ≥ 1 platinum-containing regimen

  • Disease not amenable to curative treatment with surgery and/or radiotherapy

• Must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) and/or a serum cancer antigen 125 (CA-125) level that is rising and meets 1 of the following criteria:

  • Serum CA-125 level greater than (>) upper limit of normal (typically 35 μ/mL) on two evaluations at least 2 weeks apart
  • Serum CA-125 level less than (<) 35 μ/mL but has risen progressively > 200% over successive specimens ≥ 2 weeks apart

• Estrogen receptor-positive tumor

• Gynecologic Oncology Group (GOG) performance status 0-3

• Platelet count ≥ 50 x 10^9/Liter

• Serum creatinine less than or equal to (≤) 2.5 mg/deciliter

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times upper limit of normal (ULN)

• alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

• Alkaline phosphatase ≤ 3 times ULN

• Prothrombin time-International Normalized Ratio (INR) ≤ 1.6

• Not pregnant or nursing

• Negative pregnancy test

• Must be sterile or fertile patients must use effective contraception (i.e., double method including ≥ 1 barrier, injectable, implantable, condoms plus spermicide)

• Prior malignancy allowed provided the patient has been disease-free for ≥ 5 years

  • Patients with previously diagnosed basal cell skin cancer are eligible immediately after completing therapy

• No history of bleeding (i.e., disseminated intravascular coagulation or clotting factor deficiency)

• No documented sensitivity to active or inactive excipients of fulvestrant (i.e., castor oil or mannitol)

• Recovered from the effects of prior surgery, radiotherapy, and/or chemoradiotherapy

• At least 3 weeks since prior chemotherapy

• At least 3 weeks since prior complete radiotherapy regimen alone or chemoradiotherapy

  • An incomplete radiotherapy regimen (< 500 Gray) is allowed within the 3-week time frame

Exclusion Criteria:

• Concurrent hormone replacement therapy
• Prior long-term anticoagulation therapy other than anti-platelet therapy