Fulvestrant in Treating Patients With Recurrent Ovarian Epithelial Cancer

Phase 2

Completed

Conditions: Ovarian Cancer

Interventions: Drug: Fulvestrant

Registration Number: NCT00617188

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 26

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fulvestrant	Fulvestrant	Fulvestrant 500 milligrams (mg) Day 1; 250 mg Day 1, 29 and every 28 days thereafter.

Primary Outcome Measures

Name	Time	Method
Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)	Day 90	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.

Secondary Outcome Measures

Name	Time	Method
Urine N-telopeptide Concentration	Baseline, 1 Month, 3 Months, 6 Months	Median bone mineral results - assessed by serial urine N-telopeptide laboratory results collected from patients.
Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin)	Day 90	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.
Median Number of Days to Treatment Termination	Up to 373 Days	Time is determined from first dose to termination due to all causes.
Mean Scores - Quality of Life Assessment	Baseline, 3 Months Post Treatment, 6 Months Post Treatment	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.
Serum Skeletal-Specific Alkaline Phosphatase Concentration	Baseline, 1 Month, 3 Months, 6 Months	Median Bone mineral results - assessed by serum skeletal-specific alkaline phosphatase laboratory results collected from patients in study.