Fulvestrant in Treating Patients With Recurrent Ovarian Epithelial Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Trial of Fulvestrant in Treatment of Recurrent Ovarian Carcinoma

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fulvestrant<br>Fulvestrant 500 milligrams (mg) Day 1; 250 mg Day 1, 29 and every 28 days thereafter. | Drug: Fulvestrant<br>* Fulvestrant, 500 milligrams (mg) intramuscularly (IM) on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression.<br>* Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Best response recorded from the start of treatment until Day 90. Defined by the sum of the Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=disappearance of all lesions, PR=>or =30% decrease in sum of all target lesions, Progressive Disease (PD) =>or=20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin) | Defined by the sum of Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=normalization of serum CA-125 level from 2 initially elevated samples, PR=>or=50% decrease in serum CA-125 level from 2 initially elevated samples, Progressive Disease (PD)=CA-125 two times the upper limit of normal on 2 occasions (if previously normalized) OR CA-125 two times nadir (lowest value) on 2 occasions if elevated at initiation of treatment, SD=not CR, PR or PD. | Day 90 | 
| Median Number of Days to Treatment Termination | Time is determined from first dose to termination due to all causes. | Up to 373 Days | 
| Mean Scores - Quality of Life Assessment | Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O)Version 1/23/07 - This is a relative quality of life assessment; 100 = Best, 0 = Worst. It was developed and validated with cancer patients and includes physical well being, social well being, emotional well being and relationship with doctor subscales and can be summed into one total quality of life score. It is a standardized scale which collects data (scores 1-4) from 47 questions. Answers are transformed into a number between 0-100. Mean was calculated by adding up the values of the scores and dividing by the number of scores. | Baseline, 3 Months Post Treatment, 6 Months Post Treatment | 
| Serum Skeletal-Specific Alkaline Phosphatase Concentration | Median Bone mineral results - assessed by serum skeletal-specific alkaline phosphatase laboratory results collected from patients in study. | Baseline, 1 Month, 3 Months, 6 Months | 
| Urine N-telopeptide Concentration | Median bone mineral results - assessed by serial urine N-telopeptide laboratory results collected from patients. | Baseline, 1 Month, 3 Months, 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer