Cytoreductive Surgery and HIPEC in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer

Ovarian Epithelial Cancer Clinical Trial

— HIPOVA-01  

Official title:

Assessment of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03220932
• Other study ID #: 69HCL17_0342
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 30, 2019
• Est. completion date: November 30, 2022

Study information

• Verified date: October 2019
• Source: Hospices Civils de Lyon
• Contact: Naoual BARKIN, MD,PhD
• Phone: 4 78 86 23 71
• Email: naoual.bakrin[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 132
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed platinum-resistant Epithelial Ovarian Carcinoma (EOC)(clinical recurrence or persistence within 6 months of last treatment);

• White blood cells >3,500/mm3, neutrophils =1,500/mm3, platelets =100,000/mm3;

• Good renal function: serum creatinine values <1.5 mg/dl, creatinine clearance >60 ml/min;

• Performance Status =2, Karnofsky Index =70%;

• Serum bilirubin =1.5 x Upper limit of normal (UNL) 2 mg/dl;

• Prior ovarian surgery before starting study treatment;

• Covered by a Healthcare System, where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;

• Signed written informed consent obtained prior to any study-specific screening procedures.

Exclusion Criteria:

• Platinum-refractory EOC (i.e progression under platinum containing chemotherapy);

• Any prior malignancy not considered in complete remission for at least 2 years;

• Pregnancy or breastfeeding;

• Untreated central nervous system disease or symptomatic central nervous system metastasis, history or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment;

• Uncontrolled hypertension or active clinically significant cardiovascular disease;

• Females of childbearing age not using medically accepted contraceptive measures, as judged by the investigator;

• Contraindication to any drug contained in the chemotherapy regimen;

• Known contraindication to cisplatin

• Medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent;

• Any significant disease which, in the investigator's opinion, excludes the patient from the study;

• Under any administrative or legal supervision.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Epithelial Cancer

Intervention

Procedure:
• Cytoreductive surgery combined with HIPEC
Cytoreductive surgery combined with HIPEC (Cisplatin 70 mg/m2).

Drug:
• Chemotherapy and bevacizumab (CT-BEV)
Chemotherapy and bevacizumab (CT-BEV) 15 mg/kg once every 3 weeks from enrollment until disease progression (RECIST 1.1)

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire Jean Minjoz	Besançon
France	Centre Hospitalier Universitaire Jean Minjoz	Besançon
France	Centre Oscar Lambret	Lille
France	CHRU Claude Huriez	Lille
France	Centre Léon Bérard	Lyon
France	Centre Léon Bérard	Lyon
France	Institut du Cancer de Montpellier	Montpellier
France	Institut du Cancer de Montpellier	Montpellier
France	Centre Hospitalier Universitaire L'Archet II	Nice
France	Centre Hospitalier Universitaire L'Archet II	Nice
France	Centre Hospitalier Universitaire L'Archet II	Nice
France	Hôpital Européen Georges Pompidou - APHP	Paris
France	Centre Hospitalier Lyon Sud	Pierre-benite
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
France	Centre Hospitalier Universitaire de St Etienne	Saint-priest-en-jarez
France	Centre Hospitalier Universitaire de St Etienne	Saint-Priest-en-Jarez
France	Institut de Cancérologie de la Loire	Saint-Priest-en-Jarez
France	Centre Hospitalier Universitaire Hautepierre	Strasbourg
France	Centre Hospitalier Universitaire Hautepierre	Strasbourg
France	Centre Hospitalier Universitaire Hautepierre	Strasbourg
France	Institut de Cancérologie de Lorraine - Alexis Vautrin	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Overall survival	There is a follow-up period of 36 months.	From the randomization to the death or 36 months end of follow-up
Secondary	Potential treatment-related mortality	Reported only in the experimental arm (cytoreductive surgery + HIPEC)	During the first 60 postoperative days
Secondary	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
Secondary	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