Two Therapeutic Strategies in First-line in Patients With Epithelial Advanced Ovarian Cancer

Study Overview
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Brief Summary
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CHIMOVIP is a study to determine the best therapeutic strategy in patient with ovarian advanced cancer.

Detailed Description
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This is a randomized phase II study, open-label and multicentric. After initial intervention (debulking surgery or diagnostic surgery) patient will randomized in the study according to Completeness of cytoreduction (CC) score (CC0 or CC>1).

Official Title
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Randomized Study Assessing Two Strategies of First Line: a Strategy With Intraperitoneal Chemotherapy and a Strategy With Total Intravenous Strategy, in Patients With Epithelial Advanced Ovarian Cancer

Conditions
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Ovarian Cancer, Epithelial

Intervention / Treatment
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* Drug: CC0 - Carboplatin (IV) - Paclitaxel (IV)
* Drug: CC0 - Cisplatin (IP) - Epirubicin (IV)
* Drug: CC>0 - Carboplatin (IV)- Paclitaxel (IV)
* Drug: CC>0 - Cisplatin (IP/IV)- Epirubicin (IV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced (FIGO stage III or IV) invasive epithelial ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer. Pleural cytology has to be performed in patients with pleural effusion. Initial intervention : debulking surgery or diagnostic surgery in the 3 weeks before inclusion Age ≥18 and < 75 years old. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 before surgery (ECOG ≤ 1 and Lee score < 6 in patients > 70 years old). Adequate blood count (test realized in the past 14 days before inclusion) : neutrophils > 1500/mm3, platelets > 150 000/mm3. Creatinine clearance MDRD ≥ 60 mL/min Registration in a national health care system (CMU included). Signed and dated informed consent. Exclusion Criteria: FIGO stage IV extra-abdominal disease, with the exception of lymph nodes and pleural invasion. Patient having received previous chemotherapy for ovarian cancer. Left ventricular ejection fraction < 50% before chemotherapy initiation Other invasive cancer in the past 5 years (baso- and spinocellular cutaneous carcinoma with complete resection are accepted) Concomitant administration of prophylactic phenytoin or live attenuated viral vaccines such as yellow fever vaccine, Patients with known hypersensitivity to any component of study drug Patients without motivation or capacity to respect study requirements and constraints Pregnancy or breast feeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Control arm<br>Initial or interval surgery associated with 6 cycles of chemotherapy in intravenous (IV) of carboplatin and paclitaxel. The regimen of administration of the chemotherapy is as following: Carboplatin AUC 6 - IV - Day (D) 1 Paclitaxel 80mg / m² - IV - D1, D8, D15 one cycle every 3 weeks | Drug: CC0 - Carboplatin (IV) - Paclitaxel (IV)<br>* (6 cycles)<br>Drug: CC>0 - Carboplatin (IV)- Paclitaxel (IV)<br>* carboplatin (IV) - paclitaxel (IV) (3 cycles) Interval surgery Carboplatin (IV) - paclitaxel (IV) (3 cycles)<br>|
| Experimental: Experimental arm<br>Initial or interval surgery associated with 6 cycles of chemotherapy of cisplatin and epirubicin. Cisplatin is administrated in intraperitoneal (IP) if no macroscopic residual tumor at the end of the intervention (initial or interval). If evidence of macroscopic residual tumor, cisplatin is administered in IV. Epirubicin is always given in IV. Second cytoreduction surgery at mid-term of chemotherapy cycles, only in patients operable in response after 3 cycles and with persistent residual disease after initial surgery or incomplete initial staging. The regimen of administration of the chemotherapy is as following: Cisplatin 80mg / m² - IV or IP - D1 Epirubicin 60mg / m² - IV - D3 one Cycle every 3 weeks. | Drug: CC0 - Cisplatin (IP) - Epirubicin (IV)<br>* (6 cycles)<br>Drug: CC>0 - Cisplatin (IP/IV)- Epirubicin (IV)<br>* Cisplatin (IV) - Epirubicin (IV) (3 cycles) Interval surgery : if CC0: Cisplatin (IP) - Epirubicin (IV) (3 cycles) if CC>0 Cisplatin (IV)- Epirubicin (IV) (3 cycles)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete peritoneal response (pCR) | Interval debulking surgery or final evaluation peritoneal surgery | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (QLQ -C30) assessment |  | Up to 2-year (at inclusion, after 3 cycles and end of treatment) | 
| Quality of life (QLQ-OV28) assessment |  | Up to 2-year (at inclusion, after 3 cycles and end of treatment) | 
| IPSS score |  | Up to 2-year (at inclusion, after 3 cycles and end of treatment) | 
| Number of patients with treatment-related adverse events as assessed by CTCAE version 4.03 |  | 2-year | 
| Event-free survival (EFS) |  | At 5-year and 10-year | 
| Objective response rate at the various surgical step |  | Up to 2-year | 
| Overall survival (OS) |  | At 5-year and 10-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intraperitoneal, Intravenous, Completeness of cytoreduction score, Carboplatin, Epirubicin, Paclitaxel, Cisplatin