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With 4,600 new cases in France in 2012, ovarian cancer is the seventh most common cancer in women and the fourth cause of mortality by cancer. Despite a high response rate to initial treatment, most patients will relapse within 2 years. No standard treatment has yet been established for patients with recurrent ovarian cancer.
Most patients with such recurrences are currently treated with new combinations of systemic chemotherapy. A repeated laparotomy with complete cytoreduction is also an option that several authors have used to obtain median survival rates of more than 30 months.
Twenty five percent of patients experiencing relapse present with platinum-resistant recurrence, occurring less than 6 months after chemotherapy completion. Recently, Pujade et al. showed that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in this subgroup of patients with poor prognoses (16.6 months versus 13.3 months in women treated with chemotherapy alone). Three case control studies have compared systemic chemotherapy and CRS (Cytoreduction Surgery) alone versus CRS plus HIPEC in patients with recurrent disease. They showed significantly improved results with the addition of HIPEC. In the French registry that included 474 patients with recurrence and peritoneal carcinomatosis, the median PFS was 13.8 months for platinum-resistant patients and 13 months for platinum-sensitive patients. Our hypothesis is that surgery would reduce the tumor burden and consequently the number of platinum-resistant tumor clones and that HIPEC would control the microscopic residual disease by increasing the tumor cell cytotoxicity.
We assume that adding a locoregional treatment to an "Aurelia-like" systemic treatment would improve the PFS. We aim to assess the benefit of adding surgery and HIPEC to the treatment of first or second platinum-resistant recurrence compared to chemotherapy + bevacizumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cytoreductive surgery combined with HIPEC | Experimental | All patients will start with three cycles of CT-BEV 15 mg/kg, and will then be randomly. Then one cycle of monochemotherapy without bevacizumab is administered and followed by an interval CRS and HIPEC with postoperative chemotherapy and bevacizumab (CT-BEV - 15 mg/kg once every 3 weeks) until disease progression |
|
| Aurelia arm | Active Comparator | Chemotherapy and bevacizumab (CT-BEV) once every 3 weeks from enrollment until disease progression |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytoreductive surgery combined with HIPEC | Procedure | Cytoreductive surgery combined with HIPEC (Cisplatin 70 mg/m2). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | Progression will be based on RECIST V1.1 criteria performed on thoraco-abdominopelvic tomodensitometry (TDM ) assessed every 3 months. There is a follow-up period of 36 months. | Change from baseline to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | There is a follow-up period of 36 months. | From the randomization to the death or 36 months end of follow-up |
| Potential treatment-related mortality | Reported only in the experimental arm (cytoreductive surgery + HIPEC) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Naoual BARKIN, MD,PhD | Contact | 4 78 86 23 71 | +33 | naoual.bakrin@chu-lyon.fr |
| Laurent VILLENEUVE | Contact | 78 86 45 36 | +33 | laurent.villeneuve@chu-lyon.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire Jean Minjoz | Besançon | 25030 | France |
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| Chemotherapy and bevacizumab (CT-BEV) | Drug | Chemotherapy and bevacizumab (CT-BEV) 15 mg/kg once every 3 weeks from enrollment until disease progression (RECIST 1.1) |
|
| During the first 60 postoperative days |
| Potential treatment-related morbidity | Adverse events (AE) during the follow-up period: safety and tolerability will be assessed in terms of AEs, deaths, laboratory data, and vital signs. AEs will be described using MedDRA terms (version 18.0) and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 5.0). These will be collected for all randomized patients. | During the first 60 postoperative days |
| Quality of life assessment | Quality of Life will be assessed using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) for all randomized patients. | Baseline to 36 months end of follow-up |
| Centre Hospitalier Universitaire Jean Minjoz | Besançon | 25030 | France |
|
| Centre Oscar Lambret | Lille | 59000 | France |
|
| CHRU Claude Huriez | Lille | 59067 | France |
|
| Centre Léon Bérard | Lyon | 69008 | France |
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| Centre Léon Bérard | Lyon | 69008 | France |
|
| Institut du Cancer de Montpellier | Montpellier | 34298 | France |
|
| Institut du Cancer de Montpellier | Montpellier | 34298 | France |
|
| Centre Hospitalier Universitaire L'Archet II | Nice | 06200 | France |
|
| Centre Hospitalier Universitaire L'Archet II | Nice | 06200 | France |
|
| Centre Hospitalier Universitaire L'Archet II | Nice | 06200 | France |
|
| Hôpital Européen Georges Pompidou - APHP | Paris | 75015 | France |
|
| Centre Hospitalier Lyon Sud | Pierre-Bénite | 69495 | France |
|
| Centre Hospitalier Lyon Sud | Pierre-Bénite | France |
|
| Centre Hospitalier Universitaire de Poitiers | Poitiers | 86021 | France |
|
| Centre Hospitalier Universitaire de St Etienne | Saint-Priest-en-Jarez | 42270 | France |
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| Centre Hospitalier Universitaire de St Etienne | Saint-Priest-en-Jarez | 42270 | France |
|
| Institut de Cancérologie de la Loire | Saint-Priest-en-Jarez | 42270 | France |
|
| Centre Hospitalier Universitaire Hautepierre | Strasbourg | 67200 | France |
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| Centre Hospitalier Universitaire Hautepierre | Strasbourg | 67200 | France |
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| Centre Hospitalier Universitaire Hautepierre | Strasbourg | 67200 | France |
|
| Institut de Cancérologie de Lorraine - Alexis Vautrin | Vandœuvre-lès-Nancy | 54519 | France |
|
| ID | Term |
|---|---|
| D000077216 | Carcinoma, Ovarian Epithelial |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D010051 | Ovarian Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D000084262 | Hyperthermic Intraperitoneal Chemotherapy |
| D004358 | Drug Therapy |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D017024 | Chemotherapy, Adjuvant |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D006979 | Hyperthermia, Induced |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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