S0009 Combination Chemo and Surgery in Stage III or Stage IV Ovarian Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining chemotherapy with surgery may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and surgery in treating patients who have stage III or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Detailed Description
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OBJECTIVES: Evaluate the overall survival and progression-free survival in patients with stage III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer treated with neoadjuvant paclitaxel and carboplatin followed by surgery and adjuvant paclitaxel and carboplatin. Estimate the percentage of these patients whose disease is successfully cytoreduced to less than 1 cm in diameter following neoadjuvant chemotherapy. Evaluate the toxicity of this regimen in these patients. Explore the relationship between tumor p53 expression, proliferation rate as measured by proliferating cell nuclear antigen and apoptotic rate, and human tumor cloning assay results at time of debulking surgery with progression-free survival and overall survival in these patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive neoadjuvant therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 35 days of receiving the third course of chemotherapy, patients with at least a 50% reduction in CA 125 undergo debulking surgery. Within 35 days of undergoing surgery, patients with a tumor reduction to below 1 cm receive adjuvant therapy comprising paclitaxel IV over 3 hours followed by carboplatin intraperitoneally (IP) on day 1 and paclitaxel IP on day 8. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 5 years. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 3 years.

Official Title
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Phase II Evaluation Of Neoadjuvant Chemotherapy, Interval Debulking Followed By Intraperitoneal Chemotherapy In Women With Stage III And IV Epithelial Ovarian Cancer, Fallopian Tube Cancer Or Primary Peritoneal Cancer

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer Adenocarcinoma Large pelvic mass and/or bulky abdominal disease and/or malignant pleural effusion Pleural effusion only for stage IV (parenchymal, liver, lung, or other distant metastases not allowed) No borderline or low-malignant potential tumors Optimal cytoreduction clinically deemed unlikely CA 125 at least 70 units/mL PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT no greater than 2 times ULN Renal: Creatinine clearance at least 50 mL/min Cardiovascular: No congestive heart failure or cardiac arrhythmia No myocardial infarction or angina within past 6 months Other: Not pregnant or nursing Fertile patients must use effective contraception No severe gastrointestinal symptoms (i.e., partial obstruction) and/or gastrointestinal bleeding No grade 2 or greater sensory neuropathy No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer in complete remission No active or uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for this cancer Chemotherapy: No prior chemotherapy for this cancer Endocrine therapy: Not specified Radiotherapy: No prior pelvic radiation for this cancer Surgery: See Disease Characteristics Prior exploratory laparotomy allowed provided an aggressive tumor debulking procedure was not performed (e.g., bilateral salpingo-oophorectomy/total abdominal hysterectomy with omentectomy) Prior salpingo-oophorectomy and/or partial omentectomy allowed Other: No other concurrent anti-cancer therapy

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemo/debulking surgery/IP chemo<br>neoadjuvant chemotherapy (carboplatin and paclitaxel) followed by debulking surgery followed by intraperitoneal chemotherapy (carboplatin and paclitaxel) | Drug: carboplatin<br>* pre-surgery - target AUC=6, Day 1 IV, q 21 days X 3 cycles post-surgery - target AUC=5, Day 1 IP, q 28 days X 6 cycles<br>* Other names: carbo;Drug: paclitaxel<br>* pre-surgery - 175 mg/m2 IV Day 1, q 21 days X 3 cycles post-surgery - 175 mg/m2 IV Day 1, q 28 days X 6 cycles AND 60 mg/m2 IP Day 8, q 28 days X 6 cycles<br>* Other names: Taxol;Procedure: debulking surgery<br>* exploratory laparotomy, interval cytoreduction (to < 1 cm residual)<br>* Other names: laparotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from the date of registration until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. Patients were followed every 3 months for the first year, every 6 months for years 2 and 3, and then annually for years 4 and 5. | assessed every 3 months for 1st year, then every 6 months for 2 years, then annually for years 4 and 5 | 
| Progression-Free Survival | Progression was defined as a CA-125 value that is both twice the nadir since registration and greater than 70 units/ml, and is confirmed by a second determination at least 7 days apart, or appearance of any new lesion/site. Symptomatic deterioration was defined as a global deterioration of health status requiring removal from protocol treatment. Progression-Free Survival was defined as the time from the date of registration to the date of progression, symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at last contact date. | Monthly during protocol treatment, then every 3 months up to the end of Year 1, then every 6 months for the next two years, then annually up to Year 5. | 

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