Retarded Surgery Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer (CHRONO)

CHRONO - Retarded Surgery Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

The aim of CHRONO trial is to compare the DFS when surgery is performed after 3 courses of NACT, or after 6 courses of NACT, in a prospective multi institutional randomized setting,considering only patients initially unsuitable for primary surgery.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV; Ovarian Cancer Stage IIIb
• Intervention / Treatment: Procedure: Standard IDS (Interval Debulking Surgery); Procedure: Retarded IDS (Interval Debulking Surgery)

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mihary ANDRIAMAMONJY; Phone Number: +33(0)-1-84-85-20-09; Email: mandriamamonjy@arcagy.org

Study Locations

• France
  • Angers, France, 49055
    • Active, not recruiting
    • ICO Paul Papin
  • Avignon, France, 84000
    • Recruiting
    • ICA - Polyclinique Urbain V
    • Principal Investigator: Jean-Claude DARMON
  • Beauvais, France, 60000
    • Not yet recruiting
    • Hôpital de Beauvais
    • Principal Investigator: Albine MANCAUX
  • Bordeau, France, 33076
    • Terminated
    • Institut Bergonié
  • Brest, France, 29200
    • Recruiting
    • Hôpital Morvan - Centre Hospitalier Universitaire
    • Principal Investigator: Pierre-François DUPRE
  • Caen, France, 14000
    • Recruiting
    • Centre Francois Baclesse
    • Principal Investigator: Sandrine MARTIN-FRANCOISE
  • Caen, France, 14033
    • Recruiting
    • Centre Hospitalier Universitaire Caen
    • Principal Investigator: Raffaèle FAUVET
  • Clermont-ferrand, France, 63000
    • Recruiting
    • Centre Jean Perrin
    • Principal Investigator: Christophe POMEL
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Francois Leclerc
    • Principal Investigator: Hélène COSTAZ
  • Eaubonne, France, 95602
    • Active, not recruiting
    • Hôpital Simone Veil
  • Grenoble, France, 38043
    • Active, not recruiting
    • CHU Grenoble-Alpes - Site Nord (La Tronche)
  • Le Mans, France, 72000
    • Recruiting
    • Centre Jean Bernard - Clinique Victor Hugo
    • Principal Investigator: Hugues BOURGEOIS
  • Limoges, France, 87000
    • Recruiting
    • CHU de Limoges - Hôpital de la Mère et de l'Enfant
    • Principal Investigator: Tristan GAUTHIER
  • Lorient, France, 56100
    • Recruiting
    • Hôpital du Scorff
    • Principal Investigator: Isabelle CUMIN
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Principal Investigator: Pierre MEEUS
  • Marseille, France, 13008
    • Recruiting
    • Hôpital Saint-Joseph
    • Principal Investigator: Elisabeth CHEREAU-EWALD
  • Montpellier, France, 34298
    • Recruiting
    • ICM Val D'Aurelle
    • Principal Investigator: Pierre-Emmanuel COLOMBO
  • Nantes, France, 44202
    • Active, not recruiting
    • Hôpital Privé du Confluent
  • Nantes, France, 44093
    • Terminated
    • Centre Hospitalier Universitaire de Nantes-Hôpital Mère et Enfant
  • Neuilly-sur-seine, France, 92200
    • Active, not recruiting
    • Clinique Hartmann
  • Nice, France, 06189
    • Recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Yann DELPECH
  • Paris, France, 75014
    • Recruiting
    • Hopital Cochin
    • Principal Investigator: Bruno BORGHESE
  • Paris, France, 75015
    • Recruiting
    • Hopital Europeen Georges Pompidou
    • Principal Investigator: Anne-Sophie BATS
  • Paris, France, 75651
    • Recruiting
    • Groupe Hospitalier Pitie Salpetriere
    • Principal Investigator: Catherine UZAN
  • Paris, France, 75970
    • Recruiting
    • Hopital Tenon
    • Principal Investigator: Emile DARAI
  • Pierre-benite, France, 69495
    • Not yet recruiting
    • HCL - Centre Hospitalier Lyon Sud
    • Principal Investigator: Naouel BAKRIN
  • Poitiers, France, 86021
    • Recruiting
    • Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers
    • Principal Investigator: Sheik EMAMBUX
  • Reims, France, 51056
    • Recruiting
    • Institut Jean Godinot
    • Principal Investigator: Aude-Marie SAVOYE
  • Rennes, France, 35203
    • Active, not recruiting
    • CHU de Rennes - Hôpital Sud
  • Romans-sur-Isère, France, 26100
    • Active, not recruiting
    • Hôpitaux Drôme Nord - Site de Romans-sur-Isère
  • Saint-cloud, France, 92210
    • Recruiting
    • Hôpital René Huguenin, Institut Curie
    • Principal Investigator: Claire BONNEAU
  • Saint-herblain, France, 44805
    • Recruiting
    • ICO Centre Rene Gauducheau
    • Principal Investigator: Jean-Marc CLASSE
  • Sainte Foy-les-Lyon, France, 69110
    • Recruiting
    • Clinique Médico-chirurgicale CHARCOT
    • Principal Investigator: Nicolas CARRABIN
  • Strasbourg, France, 67098
    • Not yet recruiting
    • Hopital de Hautepierre
    • Principal Investigator: Cherif Youssef AZER AKLADIOS
  • Toulouse, France, 31059
    • Recruiting
    • Institut Claudius Regaud
    • Principal Investigator: Gwénaël FERRON
  • Tours, France, 37000
    • Recruiting
    • Centre Hospitalier Universitaire Bretonneau
    • Principal Investigator: Lobna Ouldamer
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
    • Principal Investigator: Sébastien GOUY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients ≥18 years.
2. Histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma, high grade serous or endometrioïd, with the exception of mucinous, clear cell and carcinosarcoma histologies.
3. Performance status < 2 (see Appendix 2).
4. Documented International Federation of Gynecologic Oncology (FIGO 2014, Appendix 1) stage IIIB-IIIC-IVa unsuitable for complete primary cytoreductive surgery (confirmed by open laparoscopy or by laparotomy [not mandatory for stage IVA]).
5. Patient must be judged resectable after 3 courses of Neoadjuvant chemotherapy

6. Adequate bone marrow, liver and renal function to receive chemotherapy and subsequently to undergo surgery:

   • White blood cells (WBC) >3x109/L, absolute neutrophil count (ANC) ≥1,5x109/L, platelets (PLT)

     ≥100x109/L, hemoglobin (Hb) ≥9 g/dL,

   • Serum creatinine <1.25 x upper normal limit (UNL) or creatinine clearance ≥ 30 mL/min according to Cockroft-Gault formula or to local lab measurement, serum bilirubin <1.25 x UNL, AST(SGOT) and ALT(SGPT) <2.5 x UNL.
7. Signed informed consent obtained prior to any study-specific procedures.
8. Patient affiliated to, or a beneficiary of, a social security category

Exclusion Criteria:

1. Mucinous, clear cell , carcinosarcoma and low grade serous carcinomahistologies.
2. Synchronous or previous other malignancies within 3 years prior to starting study treatment, with the exception of adequately treated non-melanomatous skin cancer or carcinoma in situ (of the cervix or breast or other sites).
3. Patients with brain metastases, seizure not controlled with standard medical therapy, or history of cerebrovascular accident (CVA, stroke) or transient ischemic attack (TIA) or subarachnoid hemorrhage before 6 months from the enrollment on this study.
4. Any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise the adherence to the protocol (including but not limited to impaired cardiac function or clinically significant cardiac diseases, active or uncontrolled infections, HIV-positive patients on antiretroviral therapy, uncontrolled diabetes, cirrhosis, chronic active or persistent hepatitis, impaired respiratory function requiring oxygen-dependence, serious psychiatric disorders).
5. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interval Debulking Surgery (IDS); Complete surgery after 3 courses of neoadjuvant chemotherapy (NACT)	Procedure: Standard IDS (Interval Debulking Surgery); Patient will receive 3 courses of i.v carboplatine and paclitaxel every 3 weeks followed by IDS (Interval Debulking Surgery) within 6 weeks from C3D1. After surgery patient will undergo 5 more courses of carboplatine and paclitaxel chemotherapy. Treatment accepted : Paclitaxel and carboplatin could will be administred according to the site practice and Saint-Paul-de-Vence recommendation (Joly et al, 2017): paclitaxel 175 mg/m² + carboplatin AUC 5-6, D1=D21 or; paclitaxel 80 mg/m² at J1-J8-J15 + carboplatin AUC 5-6, D1=D21 or; paclitaxel 60 mg/m² D1-D8-D15 + carboplatin AUC2 D1-D8-D15, D1= D21; Adjuvant therapy and maintenance (optional)according to national recommendations (Saint Paul de Vence)
Experimental: Retarded Interval Debulking Surgery (IDS); Complete surgery after 6 courses of neoadjuvant chemotherapy (NACT)	Procedure: Retarded IDS (Interval Debulking Surgery); Patient will receive 6 courses of i.v carboplatine and paclitaxel every 3 weeks followed by IDS (Interval Debulking Surgery) within 6 weeks from C6D1. After surgery patient will undergo 2 more courses of carboplatine and paclitaxel chemotherapy Treatment accepted : Paclitaxel and carboplatin could will be administred according to the site practice and Saint-Paul-de-Vence recommendation (Joly et al, 2017): paclitaxel 175 mg/m² + carboplatin AUC 5-6, D1=D21 or; paclitaxel 80 mg/m² at J1-J8-J15 + carboplatin AUC 5-6, D1=D21 or; paclitaxel 60 mg/m² D1-D8-D15 + carboplatin AUC2 D1-D8-D15, D1= D21; Adjuvant therapy and maintenance (optional)according to national recommendations (Saint Paul de Vence)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Disease free survival (DFS) defined as the time interval between randomization and physical or radiographic evidence of recurrence (local/distant) or second cancer or death (all causes) whichever occur first	From date of randomisation until the date of second cancer or death, which ever occurs earlier, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EORTC QLQ-C30	Health related quality of life of the patient	through study completion, up to 2 years
Pathological complete response (PCR)	Pathological response will be established using the grading system called chemotherapy response score (CRS). The response will be assessed based on the omentum microscopic review.	through study completion, up to 2 years
Overall survival (OS)	Overall survival (OS) defined as time interval between randomization and death (all causes); alive patients will be censored at the last date of news	from date of randomisation to death, assessed up to 5 years
Time for first subsequent treatment (TFST)		up to 5 years
Post-operative mortality	Post operative mortality defined as the interval between the date of debulking surgery and the date of death due to any cause occurring within the 30 day post-surgery	up to 5 months
Post-operative morbidity	Surgical morbidity defined as the interval between the date of debulking surgery and any events occurring within the 30 day post-surgery (All grades ≥ 3 according to the CTCAE v4.03 & All grades ≥ 3 according to Clavien Dindo classification)	up to 5 months
Fagotti laparoscopic score	Disease extension assessed by Fagotti score at the time of diagnosis https://www.ncbi.nlm.nih.gov/pubmed/16791447	diagnosis
CTC-AE version 4.03 adverse events	safety assessment	30 days after last treatment intake, up to 1 year
questionnaire OV28	Physical, abdominal/gastrointestinal (GI), fatigue	through study completion, up to 2 years

Collaborators and Investigators

• Sponsor: ARCAGY/ GINECO GROUP
• Investigators: Principal Investigator: Jean-Marc Classe, MD, PhD, Institut de cancerologie de l'ouest

Publications and helpful links

General Publications

• Classe JM, Ferron G, Ouldamer L, Gauthier T, Emambux S, Gladieff L, Dupre PF, Anota A. CHRONO: randomized trial of the CHROnology of surgery after Neoadjuvant chemotherapy for Ovarian cancer. Int J Gynecol Cancer. 2022 Aug 1;32(8):1071-1075. doi: 10.1136/ijgc-2021-003320.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2018
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; ovarian cancer; retarded surgery
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: GINECO-CHIR101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No