NCT03220932

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
132

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2019

Typical duration for phase_3

Geographic Reach
1 country

22 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 11, 2017

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 18, 2017

Completed
2.4 years until next milestone

Study Start

First participant enrolled

November 30, 2019

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2022

Completed
Last Updated

November 1, 2019

Status Verified

October 1, 2019

Enrollment Period

3 years

First QC Date

May 11, 2017

Last Update Submit

October 31, 2019

Conditions

Keywords

Epithelial Ovarian Cancer - Platinum-resistant - Cytoreductive surgery - HIPEC - Quality of Life

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Overall survival

    From the randomization to the death or 36 months end of follow-up

  • Potential treatment-related mortality

    During the first 60 postoperative days

  • Potential treatment-related morbidity

    During the first 60 postoperative days

  • Quality of life assessment

    Baseline to 36 months end of follow-up

Study Arms (2)

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

Procedure: Cytoreductive surgery combined with HIPEC

Aurelia arm

ACTIVE COMPARATOR

Chemotherapy and bevacizumab (CT-BEV) once every 3 weeks from enrollment until disease progression

Drug: Chemotherapy and bevacizumab (CT-BEV)

Interventions

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

Cytoreductive surgery combined with HIPEC

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

Aurelia arm

Eligibility Criteria

Age18 Years - 75 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Centre Hospitalier Universitaire Jean Minjoz

Besançon, 25030, France

Location

Centre Hospitalier Universitaire Jean Minjoz

Besançon, 25030, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

CHRU Claude Huriez

Lille, 59067, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Centre Hospitalier Universitaire L'Archet II

Nice, 06200, France

Location

Centre Hospitalier Universitaire L'Archet II

Nice, 06200, France

Location

Centre Hospitalier Universitaire L'Archet II

Nice, 06200, France

Location

Hôpital Européen Georges Pompidou - APHP

Paris, 75015, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86021, France

Location

Centre Hospitalier Universitaire de St Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Centre Hospitalier Universitaire de St Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

Centre Hospitalier Universitaire Hautepierre

Strasbourg, 67200, France

Location

Centre Hospitalier Universitaire Hautepierre

Strasbourg, 67200, France

Location

Centre Hospitalier Universitaire Hautepierre

Strasbourg, 67200, France

Location

Institut de Cancérologie de Lorraine - Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

Hyperthermic Intraperitoneal ChemotherapyDrug TherapyBevacizumab

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsOvarian NeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Chemotherapy, AdjuvantCombined Modality TherapyTherapeuticsHyperthermia, InducedAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Central Study Contacts

Naoual BARKIN, MD,PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 11, 2017

First Posted

July 18, 2017

Study Start

November 30, 2019

Primary Completion

November 30, 2022

Study Completion

November 30, 2022

Last Updated

November 1, 2019

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Locations