Cyclophosphamide With or Without Celecoxib in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with celecoxib may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well giving cyclophosphamide together with celecoxib works compared to cyclophosphamide alone in treating patients with recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer.

Detailed Description
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OBJECTIVES: I. To assess the response rates in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer who are treated with oral cyclophosphamide alone or oral cyclophosphamide with celecoxib. II. To assess the time to disease progression in this group of patients. III. To further describe the toxicities of oral cyclophosphamide with or without celecoxib in the above patient population. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral cyclophosphamide once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive oral cyclophosphamide once daily and oral celecoxib twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Official Title
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Randomized Pilot Trial of Oral Cyclophosphamide Versus Oral Cyclophosphamide With Celecoxib for Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Conditions
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Fallopian Tube Cancer, Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Patients with recurrent or residual epithelial ovarian, Fallopian tube, or primary papillary peritoneal cancer, which has been histologically confirmed regardless of prior treatment Patients with measurable disease or rising CA-125 to levels at least twice normal (the CA-125 increase must be documented by two independent measurements at least 4 weeks apart) Patient must have adequate renal function documented by a creatinine < 1.5 Patients must have adequate bone marrow function as evidenced by an absolute neutrophil count of > 1.5 x 10^9/L and a platelet count > 100 x 10^9/L Patients must have a Karnofsky performance status of 60-100% Patient must be capable of understanding the nature of the trial and must give written informed consent Patients must have life expectancy of at least three months Patients with brain metastases which at the time of study enrollment are controlled and do not require treatment with corticosteroids are eligible Exclusion Patients who have had radiotherapy or chemotherapy within three weeks prior to anticipated first day of dosing (patients must be fully recovered from the acute effects of any prior chemotherapy or radiotherapy Patient with unstable or severe intercurrent medical conditions or active, uncontrolled infection Patients with history of bleeding peptic ulcer within last 3 months Patients undergoing therapy with other investigational agents (patients must have recovered from all acute effects of previously administered investigational agents and sufficient time must have elapsed since last administration to ensure the drug interactions not occur during this study Patients who are allergic to sulfa drugs Pregnant women will be excluded from this study due to the potential of harm to the fetus Patients with clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry Subjects with hypertension are eligible if their blood pressure as been normal while on a stable dose of medication for at least one year

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive oral cyclophosphamide once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cyclophosphamide<br>* Given orally<br>* Other names: Enduxan;|
| Experimental: Arm II<br>Patients receive oral cyclophosphamide once daily and oral celecoxib twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cyclophosphamide<br>* Given orally<br>* Other names: Enduxan;Drug: celecoxib<br>* Given orally<br>* Other names: YM 177;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Up to 3 years | 
| Time to Treatment Failure | Estimated using the product-limit method of Kaplan and Meier. Time to treatment failure is defined as the time from initial treatment to discontinuation of treatment for any reason, including progression of disease, treatment toxicity, and death. 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 of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 3 years | 
| Overall Survival | Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment to death from any cause. | Up to 5 years |