Fulvestrant 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