Retarded Surgery Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

Not Applicable

Active, not recruiting

• Conditions: Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IIIb; Ovarian Cancer Stage IV
• Interventions: Procedure: Retarded IDS (Interval Debulking Surgery); Procedure: Standard IDS (Interval Debulking Surgery)

• Registration Number: NCT03579394
• Lead Sponsor: ARCAGY/ GINECO GROUP

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-31
• Study First Submitted QC: 2018-06-25
• Study First Posted: 2018-07-06
• Study Start: 2018-10-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Primary Completion: 2027-06
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 211

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Retarded Interval Debulking Surgery (IDS)	Retarded IDS (Interval Debulking Surgery)	Complete surgery after 6 courses of neoadjuvant chemotherapy (NACT)
Interval Debulking Surgery (IDS)	Standard IDS (Interval Debulking Surgery)	Complete surgery after 3 courses of neoadjuvant chemotherapy (NACT)

Primary Outcome Measures

Name	Time	Method
Disease Free Survival	From date of randomisation until the date of second cancer or death, which ever occurs earlier, assessed up to 5 years	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

Secondary Outcome Measures

Name	Time	Method
Fagotti laparoscopic score	diagnosis	Disease extension assessed by Fagotti score at the time of diagnosis https://www.ncbi.nlm.nih.gov/pubmed/16791447
questionnaire OV28	through study completion, up to 2 years	Physical, abdominal/gastrointestinal (GI), fatigue
CTC-AE version 4.03 adverse events	30 days after last treatment intake, up to 1 year	safety assessment
Pathological complete response (PCR)	through study completion, up to 2 years	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.
Post-operative mortality	up to 5 months	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
Post-operative morbidity	up to 5 months	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)
EORTC QLQ-C30	through study completion, up to 2 years	Health related quality of life of the patient
Overall survival (OS)	from date of randomisation to death, assessed up to 5 years	Overall survival (OS) defined as time interval between randomization and death (all causes); alive patients will be censored at the last date of news
Time for first subsequent treatment (TFST)	up to 5 years

Trial Locations

Locations (29)

Centre Jean Bernard - Clinique Victor Hugo; 🇫🇷 Le Mans, France

Gustave Roussy; 🇫🇷 Villejuif, France

Centre Jean Perrin; 🇫🇷 Clermont-ferrand, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

CHU de BREST - Hôpital Cavale Blanche; 🇫🇷 Brest, France

ICA - Polyclinique Urbain V; 🇫🇷 Avignon, France

Institut Bergonié; 🇫🇷 Bordeau, France

Centre François Baclesse; 🇫🇷 Caen, France

Centre Hospitalier Universitaire Caen; 🇫🇷 Caen, France

Hôpital Simone Veil; 🇫🇷 Eaubonne, France

CHU Grenoble-Alpes - Site Nord (La Tronche); 🇫🇷 Grenoble, France

CHU de Limoges - Hôpital de la Mère et de l'Enfant; 🇫🇷 Limoges, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Hôpital du Scorff; 🇫🇷 Lorient, France

Hôpital Saint-Joseph; 🇫🇷 Marseille, France

ICM Val d'Aurelle; 🇫🇷 Montpellier, France

Centre Hospitalier Universitaire de Nantes-Hôpital Mère et Enfant; 🇫🇷 Nantes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Hôpital Privé du Confluent; 🇫🇷 Nantes, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

Hôpital Cochin; 🇫🇷 Paris, France

Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers; 🇫🇷 Poitiers, France

Institut Jean Godinot; 🇫🇷 Reims, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Groupe Hospitalier Pitié Salpétrière; 🇫🇷 Paris, France

Clinique Médico-chirurgicale CHARCOT; 🇫🇷 Sainte Foy-les-Lyon, France

Hôpital René Huguenin, Institut Curie; 🇫🇷 Saint-cloud, France

ICO Centre René Gauducheau; 🇫🇷 Saint-herblain, France

Centre Hospitalier Universitaire Bretonneau; 🇫🇷 Tours, France