Mifepristone in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Study Overview
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Brief Summary
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RATIONALE: Progesterone can cause the growth of ovarian epithelial cancer , primary peritoneal cancer, or fallopian tube cancer. Hormone therapy using mifepristone may fight ovarian epithelial cancer and primary peritoneal cancer by lowering the amount of progesterone the body makes. PURPOSE: This phase II trial is studying the side effects and how well mifepristone works in treating patients with recurrent or persistent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of mifepristone in patients with recurrent or persistent ovarian epithelial, primary peritoneal, or fallopian tube carcinoma. Determine the toxicity of this drug in these patients. Secondary Determine the duration of progression-free survival and overall survival of patients treated with this drug. Determine the potential impact of platinum sensitivity, initial performance status, and age on prognosis in these patients. OUTLINE: This is a multicenter study. Patients receive oral mifepristone once daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

Official Title
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A Phase II Evaluation of Mifepristone in the Treatment of Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: mifepristone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube carcinoma* Recurrent or refractory disease NOTE: *Histological confirmation of original primary tumor required Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, and MRI OR ≥ 10 mm by spiral CT scan Must have ≥ 1 target lesion Tumors within a previously irradiated field are designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiotherapy Prior treatment with 1 platinum-based chemotherapeutic regimen (comprising carboplatin, cisplatin, or another organoplatinum compound) for management of primary disease required Initial treatment may have included any of the following: High-dose therapy Consolidation therapy Extended therapy administered after surgical or nonsurgical assessment Patients must meet ≥ 1 of the following criteria: Treatment-free interval after platinum therapy of < 12 months Progressed during platinum-based therapy Persistent disease after a platinum-based regimen Not eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists PATIENT CHARACTERISTICS: GOG performance status 0-2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN AST ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN No active infection requiring antibiotics No other invasive malignancies within the past 5 years, except non-melanoma skin cancer PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior surgery, radiotherapy, or chemotherapy No prior cancer treatment that would preclude protocol therapy No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of ovarian cancer Prior radiotherapy for localized cancer of the breast, head and neck, or skin is permitted, provided it was completed > 3 years prior to study entry and no recurrent or metastatic disease exists No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of ovarian cancer Prior chemotherapy for localized cancer of the breast is permitted, provided it was completed > 3 years prior to study entry and no recurrent or metastatic disease exists At least 1 week since prior hormonal therapy directed at the malignant tumor At least 2 weeks since other prior hormonal therapy (e.g., testosterone, estrogen, progestin, or gonadotropin-releasing hormone antagonists) At least 3 weeks since other prior therapy directed at the malignant tumor, including biological or immunologic agents One prior cytotoxic regimen (defined as any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa) for management of recurrent or persistent disease allowed No prior non-cytotoxic therapy for management of recurrent or persistent ovarian epithelial or primary peritoneal carcinoma No prior mifepristone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mifepristone 200 mg PO daily<br>Mifepristone 200 mg PO daily administered on a continuous basis (every 4 weeks is considered one cycle) until disease progression or adverse effects prohibit further therapy. | Drug: mifepristone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival at 6 Months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 
| Proportion of Patients With Objective Tumor Response | Complete and Partial Tumor Response by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Per RECIST v1.0 for target lesions and assessed by MRIor CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 
| Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 |  | Every cycle, during treatment (average of 3 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 
| Overall Survival |  | Five years | 
| Progression-free Survival by Platinum Sensitivity | Platinum Senstive defined as treatment free interval >6 months on most recent platinum | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 
| Progression-free Survival by Performance Status |  | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 
| Progression-free Survival by Age (y) | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. | Every other cycle, for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, fallopian tube cancer