Intraperitoneal Therapy For Ovarian Cancer With Carboplatin Trial

Study Overview
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Brief Summary
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The purpose of this study is: Phase A: To confirm the feasibility of paclitaxel administered by intravenous (IV) infusion weekly plus concurrent carboplatin administered by intraperitoneal (IP) injection once every 3 weeks (dd-TCip therapy). Phase B: To compare the efficacy and safety of the following two treatment regimens as first-line chemotherapy in women with epithelial ovarian, Fallopian tube or primary peritoneal cancer.

Detailed Description
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This is a randomized, multicenter international study. Patient are stratified according to Residual tumor diameter([0cm(No residual)] vs. [0cm<residual<1cm] vs. [1cm<residual<2cm] vs. [>2 cm]), FIGO stage(StageII vs. III vs. IV) and institution. Patient randomized to one of the treatment arms described below. RegimenI(Standard treatment: dd-TCiv therapy): Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IV infusion once every 3 weeks RegimenII(Study treatment: dd-TCip therapy): Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IP injection once every 3 weeks The 3-week period (21 days) is 1 cycle. Protocol treatment basically comprises 6 cycles. IDS is allowed to be performed after 3, 4 or 5 cycles of the protocol treatment. In such cases, the protocol treatment must be restarted within 8 weeks after IDS. If IDS is performed, patients can receive up to 3 additional cycles of the protocol treatment after IDS. If interval debulking surgery (IDS) is performed after 3, 4 or 5 cycles, the patients can receive up to 3 additional cycles of the protocol treatment. A total of 6 to 8 cycles will be repeated. The analysis of efficacy will be performed on all randomized subjects in accordance with the intention-to-treat (ITT) principle. In order to assess the robustness of the results, the same analyses will be done using all randomized subjects who satisfy the eligibility criteria. The analysis of safety will be performed on all subjects who have received at least one dose of study treatment.

Official Title
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A Randomized Phase II/III Trial of Intravenous (IV) Paclitaxel Weekly Plus IV Carboplatin Once Every 3 Weeks Versus IV Paclitaxel Weekly Plus Intraperitoneal (IP) Carboplatin Once Every 3 Weeks in Women With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Conditions
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Primary Peritoneal Carcinoma, Epithelial Ovarian Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: Paclitaxel(intravenous) + Carboplatin(intravenous)
* Drug: Paclitaxel(intravenous) + Carboplatin(intraperitoneal)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients assumed to have a stageII-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer as a pre-surgery diagnosis Patients scheduled to undergo laparotomy *Both optimal and suboptimal patients will be eligible for the study (Suboptimal patients, as well as those who undergo only exploratory laparotomy, are eligible.) ECOG Performance Status: 0-2 Patients who provide consent for placement of the IP port system, if randomized to Regimen II (Study treatment: dd-TCip therapy) Patients expected to receive the first protocol treatment within 8 weeks after the comprehensive staging surgery Lab data and clinical examination: Data within 28 days before the scheduled date of surgery Neutrophil count ≧ 1,500 /mm3 Platelet count ≧ 100,000 /mm3 AST (GOT) ≦ 100 IU/L ALT (GPT) ≦ 100 IU/L Total bilirubin < 1.5 mg/dL Serum Creatinine < 1.5 mg/dL Electrocardiogram (ECG): Patients with normal ECG, Asymptomatic patients with abnormal ECGs not requiring medical intervention Neuropathy(Both motor and sensory) ≦ Grade1 (CTCAE Version 4.0) Patients expected to survive longer than 3 months from the start date of the protocol treatment Patients aged 20 years and older at the time of tentative registration (with no upper age limit) Patients who provide written informed consent for participation in this trial Exclusion Criteria: Patients assumed to have a borderline malignancy of the ovary, fallopian tube, or primary peritoneal cancer Patients who have received previous chemotherapy or radiation therapy to treat the current disease Patients who have a synchronous malignancy or who have been progression-free less than 5 years for a metachronous malignancy (Patients with basal and squamous cell carcinoma of the skin, as well as carcinoma in situ, and intramucosal carcinoma cured by local treatment, are eligible for the study) Patients with serious medical complications, such as serious heart disease, cerebrovascular accidents, uncontrolled diabetes mellitus, uncontrolled hypertension, pulmonary fibrosis, interstitial pneumonitis, active bleeding, an active gastrointestinal ulcer, or a serious neurological disorder Patients who have had a hypersensitivity reaction to polyoxyethylated or hydrogenated castor oil Patients with a pleural effusion requiring continuous drainage Patients with an active infection requiring antibiotics Patients who are pregnant, nursing or of child-bearing potential Patients with evidence upon physical examination of brain tumor and any brain metastases Patients for whom completion of this study and/or follow-up is deemed inappropriate for any reason Patients with any signs/symptoms of interstitial pneumonia

Ages Eligible for Study
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Minimum Age: 20 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: Standard treatment: dd-TCiv therapy<br>Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IV infusion once every 3 weeks | Drug: Paclitaxel(intravenous) + Carboplatin(intravenous)<br>* Paclitaxel(intravenous) + Carboplatin(intravenous) Paclitaxel : 80mg/m2, IV infusion, Day1, 8, and 15 Carboplatin: AUC=6.0, IV infusion, Day1 A total of 6 to 8 cycles will be repeated.<br>* Other names: Paclitaxel(Sawai),(NK), Paraplatin(BMS), Carboplatin(SANDOZ);|
| Experimental: Study treatment: dd-TCip therapy<br>Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IP injection once every 3 weeks | Drug: Paclitaxel(intravenous) + Carboplatin(intraperitoneal)<br>* Paclitaxel(intravenous) + Carboplatin(intraperitoneal) Paclitaxel : 80mg/m2, IV infusion, Day1, 8, and 15 Carboplatin: AUC=6.0, IP injection, Day1 A total of 6 to 8 cycles will be repeated.<br>* Other names: Paclitaxel(Sawai),(NK), Paraplatin(BMS), Carboplatin(SANDOZ);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival(PFS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed until 510 events are observed or until 3 years from the last patient is randomized to the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | weekly during the protocl treatment, then every 3 months for the first 2 years, 6-month for the following 2 years, and once a year thereafter | 
| Tumor response (only patients with evaluable disease) |  | every 2 cycles [after 2 cycles, after 4 cycles, after 6 cycles, (after 8 cycles)], the time of discontinuation of the protocol treatment and then at least annually during follow-up | 
| Adverse events |  | weekly during the protocl treatment, then every 3 months for the first 2 years, 6-month for the following 2 years, and once a year thereafter | 
| Treatment completion rate |  | After the last cycle of the protocol teatment | 
| Quality of Life (QOL) assessments |  | baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment | 
| Cost-utility analysis |  | baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epithelial ovarian cancer, Fallopian tube cancer, peritoneal cancer, intraperitoneal therapy, Carboplatin, Paclitaxel