Retarded Surgery Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

Ovarian Cancer Stage IV Clinical Trial

— CHRONO  

Official title:

CHRONO - Retarded Surgery Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03579394
• Other study ID #: GINECO-CHIR101
• Status: Recruiting
• Phase: N/A
• Start date: October 19, 2018
• Est. completion date: July 2028

Study information

• Verified date: December 2023
• Source: ARCAGY/ GINECO GROUP
• Contact: Mihary ANDRIAMAMONJY
• Phone: +33(0)-1-84-85-20-09
• Email: mandriamamonjy[@]arcagy.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: July 2028
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer Stage IIIb
• Ovarian Cancer Stage IIIC
• Ovarian Cancer Stage IV
• Ovarian Neoplasms

Intervention

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)
• 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)

Locations

Country	Name	City	State
France	ICO Paul Papin	Angers
France	ICA - Polyclinique Urbain V	Avignon
France	Hôpital de Beauvais	Beauvais
France	Institut Bergonié	Bordeau
France	Hôpital Morvan - Centre Hospitalier Universitaire	Brest
France	Centre François Baclesse	Caen
France	Centre Hospitalier Universitaire Caen	Caen
France	Centre Jean Perrin	Clermont-ferrand
France	Centre Georges François Leclerc	Dijon
France	Hôpital Simone Veil	Eaubonne
France	CHU Grenoble-Alpes - Site Nord (La Tronche)	Grenoble
France	Centre Jean Bernard - Clinique Victor Hugo	Le Mans
France	CHU de Limoges - Hôpital de la Mère et de l'Enfant	Limoges
France	Hôpital du Scorff	Lorient
France	Centre Léon Bérard	Lyon
France	Hôpital Saint-Joseph	Marseille
France	ICM Val d'Aurelle	Montpellier
France	Centre Hospitalier Universitaire de Nantes-Hôpital Mère et Enfant	Nantes
France	Hôpital Privé du Confluent	Nantes
France	Clinique Hartmann	Neuilly-sur-seine
France	Centre Antoine Lacassagne	Nice
France	Groupe Hospitalier Pitié Salpétrière	Paris
France	Hôpital Cochin	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Tenon	Paris
France	HCL - Centre Hospitalier Lyon Sud	Pierre-benite
France	Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers	Poitiers
France	Institut Jean Godinot	Reims
France	CHU de Rennes - Hôpital Sud	Rennes
France	Hôpitaux Drôme Nord - Site de Romans-sur-Isère	Romans-sur-Isère
France	Hôpital René Huguenin, Institut Curie	Saint-cloud
France	ICO Centre René Gauducheau	Saint-herblain
France	Clinique Médico-chirurgicale CHARCOT	Sainte Foy-les-Lyon
France	Hôpital de Hautepierre	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Centre Hospitalier Universitaire Bretonneau	Tours
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
ARCAGY/ GINECO GROUP

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	EORTC QLQ-C30	Health related quality of life of the patient	through study completion, up to 2 years
Secondary	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
Secondary	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
Secondary	Time for first subsequent treatment (TFST)		up to 5 years
Secondary	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
Secondary	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
Secondary	Fagotti laparoscopic score	Disease extension assessed by Fagotti score at the time of diagnosis https://www.ncbi.nlm.nih.gov/pubmed/16791447	diagnosis
Secondary	CTC-AE version 4.03 adverse events	safety assessment	30 days after last treatment intake, up to 1 year
Secondary	questionnaire OV28	Physical, abdominal/gastrointestinal (GI), fatigue	through study completion, up to 2 years