Carboplatin, Paclitaxel, and Surgery in Treating Patients With Advanced Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Giving chemotherapy drugs before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving paclitaxel together with carboplatin before surgery works in treating patients with advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed Description
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OBJECTIVES: Primary Determine whether at least 50% of patients with advanced ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer are able to achieve optimal cytoreduction (to < 1 centimeter of remaining disease) after neoadjuvant chemotherapy comprising paclitaxel and carboplatin. Secondary Determine the frequency and severity of toxicity associated with this regimen in patients who are high-risk surgical candidates or in patients unlikely to achieve optimal surgical cytoreduction. Determine if extreme drug resistance assay profiles change after neoadjuvant chemotherapy. Determine how thrombospondin-1 (TSP-1), tumor protein 53 (p53), and tumor vessel density change after administration of neoadjuvant chemotherapy. Assess the quality of life of patients receiving neoadjuvant chemotherapy. Obtain estimates of tumor response after administration of neoadjuvant chemotherapy. Determine whether serum cancer antigen 125 (CA-125) at the time of cytoreduction is associated with the ability to optimally reduce the patients. OUTLINE: This is an open-label study. Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after the fourth course of chemotherapy, patients undergo interval cytoreductive surgery. Patients who are unable to undergo surgery receive 2 additional courses of chemotherapy and are re-evaluated for surgery after the sixth course of chemotherapy. Within 4 weeks after surgery, patients receive 2 additional courses of chemotherapy. Quality of life is assessed periodically. Tumor samples are obtained via laparoscopic or percutaneous biopsy prior to beginning chemotherapy and during interval cytoreduction. Tissue is examined by immunohistochemistry staining for p53, TSP-1, microvessel density (CD31), angiogenesis, membrane protein BCL-2, and multidrug resistant gene 1 (MDR-1). Gene array analysis and extreme drug resistant assays are also performed. After completion of study treatment, patients are followed every 3 months for 2 years.

Official Title
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A Phase II Study of Carboplatin and Paclitaxel as Neoadjuvant Chemotherapy Followed by Interval Cytoreduction in Women With Advanced Staged Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma for High-Risk Surgical Candidates or Patients Unlikely to be Optimally Surgically Cytoreduced

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Procedure: cytoreductive surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histological diagnosis of epithelial ovarian, primary peritoneal, or fallopian tube carcinoma for which no previous treatment has been given. Patients with the following histological epithelial cell types are eligible: Serous adenocarcinoma Mucinous adenocarcinoma Clear cell adenocarcinoma Transitional cell Adenocarcinoma not otherwise specified Endometrioid adenocarcinoma Undifferentiated carcinoma Mixed epithelial carcinoma Malignant Brenner's tumor Measurable or non-measurable disease as defined by Solid Tumor Response Criteria (RECIST) within 4 weeks of study entry High-risk surgical candidate Gynecologic Oncology Group (GOG) performance status 0-3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 1.5 mg/dL Alkaline phosphatase ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times ULN Life expectancy ≥ 12 weeks Exclusion Criteria: Pregnant or nursing Positive pregnancy test -(Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment.) History of another neoplasm except for non-metastatic, non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery > 5 years prior to registration. Septicemia, severe infection, acute hepatitis, or severe gastrointestinal bleeding, defined as requiring blood transfusion or hospitalization at registration Unstable angina will not be eligible. Patients with evidence of abnormal cardiac conduction (e.g. bundle branch block, heart block) are eligible if their disease has been stable for the past six months. History of severe hypersensitivity or allergic reaction to study drugs, drugs formulated in Cremophor EL^®, other platinol compounds, or mannitol

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients Who Received Treatment<br>All patients receiving treatment with Paclitaxel and Carboplatin followed by surgery to remove cancerous tissue. | Drug: carboplatin<br>* Carboplatin dose (milligrams (mg)) - Target Area Under the Curve (AUC) 6 x (Glomerular Filtration Rate+25) - Calvert Formula, given intravenously (IV) for 30 minutes.<br>* Other names: Paraplatin;Drug: paclitaxel<br>* Paclitaxel dose = 175 milligrams per meter squared (mg/m2) over 3 hours.<br>* Other names: Taxol;Procedure: cytoreductive surgery<br>* Surgery - tumor specimen collected for extreme drug resistant assay (EDR) and A1 assays for analysis<br>* Other names: debulking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy | These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response. | Week 18 (After 4 cycles of chemotherapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. | Week 16 (4 weeks after 4th course) | 
| Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration | Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response. | From Baseline to up to 12 weeks (4 courses of therapy) | 
| Change in Drug Resistance After Neoadjuvant Chemotherapy | As measured by extreme drug resistance assay - Unable to report due to tissue samples being incomplete or unsatisfactory to do laboratory testing. | Day 1 to Time to Surgery (Approximately Week 18) | 
| Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density | Unable to report due to incomplete (nonviable) or unsatisfactory tissue samples. | Week 18 (At surgery) | 
| Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy | Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire was used to assess the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. It is a 5 point scale (from worse to best: 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much responses). Physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns questions are asked. Unable to evaluate; patients did not consistently complete the questionnaires. | Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian clear cell cystadenocarcinoma, ovarian endometrioid adenocarcinoma, ovarian mixed epithelial carcinoma, ovarian mucinous cystadenocarcinoma, ovarian serous cystadenocarcinoma, ovarian undifferentiated adenocarcinoma, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, peritoneal cavity cancer, fallopian tube cancer, Brenner tumor