Utility of Adjusting Chemotherapy Dose & Dosing Schedule With the SALVage Weekly Dose-dense Regimen in Patients With Poor Prognostic OVARian Cancers Based on the Tumor Unfavorable Primary Chemosensitivity and Incomplete Debulking Surgery (SALVOVAR)

A Pragmatic Randomized Phase III Trial to Assess the Utility of Adjusting Chemotherapy Dose & Dosing Schedule With the SALVage Weekly Dose-dense Regimen in Patients With Poor Prognostic OVARian Cancers Based on the Tumor Unfavorable Primary Chemosensitivity and Incomplete Debulking Surgery

SALVOVAR will be a pragmatic open-label multicenter randomized phase III trial (ratio 1:1) comparing the efficacy of the salvage weekly dose-dense regimen with those of the continuation of the standard regimen.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel

Detailed Description

SALVOVAR is a pragmatic open-label multicenter randomized phase III trial (ratio 1:1) comparing the efficacy of the salvage weekly dose-dense regimen with those of the continuation of the same standard regimen as given during neo-adjuvant period. The randomization will be stratified on the main clinical prognostic factors assumed to impact the efficacy of the assessed arms and the overall survival:

1. Bevacizumab: planned administration: Yes, vs No
2. BRCA mutation: planned administration: Yes, vs No/Unknown
3. KELIMTM strate within unfavorable KELIM subgroup: very unfavorable < 0.7, vs moderately unfavorable [0.7-1.0[

The trial will be pragmatic, as it aims at confirming the superiority of the adjusted chemotherapy compared to the continuation of the standard chemotherapy in routine clinical practice, in a population of ovarian cancer patients close to the real-life clinical activity with few selection criteria.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marine COGNAT; Phone Number: +33 1 84 85 20 20; Email: salvovar.trial@arcagy.org

Study Locations

• France
  • Angers, France, 49055
    • Recruiting
    • ICO Paul Papin
    • Contact: Sophie ABADIE-LACOURTOISIE
  • Avignon, France, 84902
    • Recruiting
    • CH d'Avignon
    • Contact: Nathan AOUIZERAT
  • Avignon, France, 84918
    • Recruiting
    • Sainte-Catherine Institut du Cancer Avignon-Provence
    • Contact: Julien GRENIER
  • Bayonne, France, 64100
    • Recruiting
    • Hopital de la cote Basque
    • Contact: Thomas GRELLETY
  • Besançon, France, 25030
    • Recruiting
    • CHRU Besancon - Hopital Jean Minjoz
    • Contact: Laura MANSI
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonie
    • Contact: Coriolan LEBRETON
  • Brest, France, 29200
    • Recruiting
    • CHU de BREST - Hôpital Cavale Blanche
    • Contact: Laura DEIANA
  • Caen, France, 14076
    • Recruiting
    • Centre Francois Baclesse
    • Contact: Florence JOLY
  • Chambray-lès-Tours, France, 37170
    • Recruiting
    • Centre d'Oncologie et de Radiothérapie 37 (ROC37)
    • Contact: Pierre COMBE
  • Cholet, France, 49300
    • Recruiting
    • Centre Hospitalier de Cholet
    • Contact: Sylvère GUILLEMOIS
  • Clermont-Ferrand, France, 63011
    • Recruiting
    • Centre Jean Perrin
    • Contact: Laure VACHER
  • Contamine-sur-Arve, France, 74130
    • Not yet recruiting
    • Centre Hospitalier Alpes Leman
    • Contact: Mansour RASTKHAH
  • Créteil, France, 94010
    • Recruiting
    • Centre Hospitalier Intercommunal de Créteil
    • Contact: Zineb SELLAM-CHORFI
  • Dijon, France, 21079
    • Recruiting
    • CHU de Dijon
    • Contact: Marie CHAIX
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges François Leclerc
    • Contact: Jean-David FUMET
  • Grenoble, France, 38028
    • Recruiting
    • Groupe hospitalier mutualiste de Grenoble
    • Contact: Elise BONNET
  • Le Chesnay, France, 78157
    • Not yet recruiting
    • Hôpital André Mignot
    • Contact: Marie-Sophie THIS
  • Lille, France, 59020
    • Not yet recruiting
    • Centre Oscar Lambret
    • Contact: Stéphanie BECOURT
  • Lille, France, 59000
    • Not yet recruiting
    • CHRU de Lille
    • Contact: Yohan KERBAGE
  • Limoges, France, 87042
    • Recruiting
    • CHU de Limoges - Hôpital Dupuytren
    • Contact: Laurence VENAT-BOUVET
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Contact: Philippe TOUSSAINT
  • Lyon, France, 69373
    • Recruiting
    • Hopital Prive Jean Mermoz
    • Contact: Olfa DERBEL MILED
  • Lyon, France, 69229
    • Not yet recruiting
    • Hopital de la croix rousse
    • Contact: Sophie DUPLOMB
  • Marseille, France, 13005
    • Not yet recruiting
    • Hopital De La Timone
    • Contact: Marie MEURER
  • Montpellier, France, 34298
    • Not yet recruiting
    • ICM Val d'Aurelle
    • Contact: Stanislas QUESADA
  • Montpellier, France, 34059
    • Not yet recruiting
    • CHRU de Montpellier - Hôpital Saint-Eloi
    • Contact: Clothilde LINDET-BOURGEOIS
  • Mougins, France, 06250
    • Recruiting
    • Centre Azuréen de Cancérologie
    • Contact: Rémy LARGILLIER
  • Nantes, France, 44202
    • Recruiting
    • Hopital prive du Confluent
    • Contact: Cyriac BLONZ
  • Nice, France, 06189
    • Recruiting
    • Centre Antoine Lacassagne
    • Contact: Philippe Follana
  • Nîmes, France, 30029
    • Recruiting
    • Institut de Cancérologie du Gard - CHU de Nîmes
    • Contact: Frédéric FITENI
  • Paris, France, 75014
    • Recruiting
    • Hôpital Cochin
    • Contact: Sixtine DE PERCIN
  • Paris, France, 75248
    • Recruiting
    • Institut Curie
    • Contact: Manuel Rodrigues
  • Paris, France, 75015
    • Not yet recruiting
    • Hôpital Européen George Pompidou
    • Contact: Claire GERVAIS
  • Paris, France, 75012
    • Recruiting
    • Groupe Hospitalier Diaconesses - Croix Saint-Simon
    • Contact: Frédéric SELLE
  • Pau, France, 64046
    • Recruiting
    • Centre Hospitalier Général de Pau
    • Contact: Kevin BOURCIER
  • Pierre-Bénite, France, 69495
    • Recruiting
    • HCL - Centre Hospitalier Lyon Sud
    • Contact: Benoit You
  • Poissy, France, 78303
    • Not yet recruiting
    • Hôpital de Poissy-Saint-Germain-en-Laye
    • Contact: Gabriela TOSSEN
  • Reims, France, 51056
    • Not yet recruiting
    • Institut Jean Godinot
  • Rennes, France, 35042
    • Recruiting
    • Centre Eugène Marquis
    • Contact: Thibault DE LA MOTTE ROUGE
  • Saint-Etienne, France, 42100
    • Not yet recruiting
    • Hôpital Privé de la Loire
    • Contact: Romain RIVOIRARD
  • Saint-Herblain, France, 44805
    • Recruiting
    • Institut de Cancérologie de l'Ouest - ICO
    • Contact: Dominique BERTON
  • Saint-Priest-en-Jarez, France, 42271
    • Recruiting
    • CHU Saint-Etienne - Pôle de Cancérologie
    • Contact: Pauline CORBAUX
  • Strasbourg, France, 67033
    • Recruiting
    • ICANS - Institut de cancérologie Strasbourg Europe
    • Contact: Lauriane EBERST
  • Strasbourg, France, 67098
    • Not yet recruiting
    • Chu Strasbourg - Hôpital de Hautepierre
    • Contact: Lauriane EBERST
  • Suresnes, France, 92151
    • Recruiting
    • Hopital Foch
    • Contact: Asmahane BENMAZIANE
  • Thonon-les-Bains, France, 74203
    • Not yet recruiting
    • Hôpitaux du Léman - site Thonon-les-Bains
    • Contact: Fanny POMMERET
  • Toulouse, France, 31300
    • Recruiting
    • Clinique Pasteur
    • Contact: Mathilde MARTINEZ
  • Toulouse, France, 31059
    • Recruiting
    • Oncopole Claudius Régaud - IUCT Oncopole
    • Contact: Gwénaël FERRON
  • Valence, France, 26953
    • Recruiting
    • Centre Hospitalier de Valence
    • Contact: Rim BATTI
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
    • Contact: Alexandra LEARY
• Italy
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria
    • Contact: Giulia Gallizzi
  • Bologna, Italy, 40138
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria di Bologna IRCCS Istituto di Ricerca e di Cura a Carattere Scientifico
    • Contact: Claudio Zamagni
  • Florence, Italy, 50134
    • Not yet recruiting
    • Careggi University Hospital
    • Contact: Maria Cristina Petrella
  • Lecco, Italy, 23900
    • Not yet recruiting
    • Alessandro Manzoni Hospital
    • Contact: Federica Villa
  • Milan, Italy, 20141
    • Not yet recruiting
    • Istituto Europeo Di Oncologia S.r.l.
    • Contact: Gabriella Maria Parma
  • Venice, Italy, 30174
    • Not yet recruiting
    • Azienda Ulss 3 Serenissima
    • Contact: Alessandra Baldoni
• Japan
  • Bunkyō City, Japan
    • Not yet recruiting
    • The University of Tokyo Hospital
    • Contact: Mayuyo MORI
  • Fukushima, Japan
    • Not yet recruiting
    • Fukushima Medical University Hospital
    • Contact: Shu SOEDA
  • Hidaka, Japan
    • Recruiting
    • Saitama Medical University International Medical Center
    • Contact: Akira YABUNO
  • Hirosaki, Japan
    • Not yet recruiting
    • Hirosaki University Hospital
    • Contact: Yoshihito YOKOYAMA
  • Kashiwa, Japan
    • Not yet recruiting
    • The Jikei University Kashiwa Hospital
    • Contact: Kunihiro TAKANO
  • Kawasaki, Japan
    • Not yet recruiting
    • St. Marianna University Hospital
    • Contact: Nao SUZUKI
  • Koshigaya, Japan
    • Not yet recruiting
    • Dokkyo Medical University Saitama Medical Center
    • Contact: Hamada Yoshinobu
  • Kurume, Japan
    • Not yet recruiting
    • Kurume University Hospital
    • Contact: Shin NISHIO
  • Nagoya, Japan
    • Not yet recruiting
    • Nagoya University Hospital
    • Contact: Nobuhisa YOSHIKAWA
  • Sayama, Japan
    • Not yet recruiting
    • Kindai University Hospital
    • Contact: Hidekatsu NAKAI
  • Sendai, Japan
    • Not yet recruiting
    • Tohoku University Hospital
    • Contact: Shogo SHIGETA
  • Takatsuki, Japan
    • Not yet recruiting
    • Osaka Medical and Pharmaceutical University Hospital
    • Contact: Masahide OHMICHI
  • Tokyo, Japan
    • Not yet recruiting
    • The Cancer Institute Hospital of JFCR
    • Contact: Hiroyuki KANAO
  • Tokyo, Japan
    • Not yet recruiting
    • The Jikei University Daisan Hospital
    • Contact: Kyosuke YAMOTO
  • Tokyo, Japan
    • Not yet recruiting
    • The Jikei University Hospital
    • Contact: Aikou OKAMOTO
  • Tokyo, Japan
    • Not yet recruiting
    • The Jikei University Katsushika Medical Center
    • Contact: Motoaki SAITO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed high-grade epithelial (serous, endometrioid, or carcinosarcoma with a ≥30% epithelial tumor component) ovarian, primary peritoneal, or fallopian-tube carcinoma
2. Adult patient aged ≥ 18 years old
3. Advanced stage III or IV disease

4. Treated with 3 to 4 neo-adjuvant cycles of standard 3-weekly carboplatin-paclitaxel regimen in first-line setting, and characterized by:

   • Unfavorable standardized KELIMTM score < 1.0 calculated with the KELIMTM academic tool and available for free on internet site (https://www.biomarker-kinetics.org/CA-125-neo) (poor primary chemosensitivity)
   • Not amenable to complete interval debulking surgery (incomplete interval debulking surgery attempt, or disease not operated at all because considered not amenable to complete surgery by surgeon) Of note, a pre-screening inclusion before the start of neo-adjuvant chemotherapy is encouraged as a way of prospectively assessing the CA-125 longitudinal kinetics and surgery evaluation, and subsequently selecting the patients for the randomization sequence
5. ECOG performance status 0 or 1 (see appendix 2)
6. Adequate organ and bone marrow function for weekly-dense chemotherapy: red blood cells (baseline Hemoglobin ≥8 g/dL without red blood cell transfusion within 3 weeks before the blood work), white blood cells (Absolute neutrophil count (ANC) ≥1500 cells/mm3) and platelets (Platelet count ≥100,000/mm3),

7. Adequate renal and liver functions

   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN in context of liver metastases
   • Total bilirubin ≤1.5 × ULN (patients with Gilbert's are eligible if total bilirubin ≤3 × ULN)
   • Albumin ≥3 g/dL
   • Creatinine clearance ≥40 mL/min/1.73 m2 (measured or estimated, ideally with CKD-EPI formula on https://www.kidney.org/professionals/kdoqi/gfr_calculator)
8. Patients who gave its written informed consent to participate to the study
9. Patients affiliated to a social insurance regime
10. Patients willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

1. Low-grade endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of these histologies, or low-grade or borderline ovarian tumor. Contraindication to the drugs assessed in the SALVOVAR trial (carboplatin, paclitaxel, GCSF)
2. Previous treatment with bevacizumab during initial standard neo-adjuvant chemotherapy
3. Has primary platinum-refractory disease, defined as disease that has progressed during the neo-adjuvant chemotherapy
4. Patients with concomitant cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
5. Treatment with other investigational agents in clinical trials.

6. Clinically significant uncontrolled condition(s) which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient's safety or participation, including but not limited to:

   • Unstable angina.
   • Myocardial infarction within 6 months of first dose.
   • Uncontrolled and/or severe concomitant diseases (uncontrolled hypertension, ≥ Grade 3 (per CTCAE v5.0) arrhythmia, heart failure, cirrhosis).
   • Active infectious disease requiring IV therapy (bacteria, viruses) within 2 weeks of first dose.
   • Gastric-outlet obstruction.
   • Small bowel obstruction (SBO) defined as computed tomography (CT) scan showing: Dilated loops of small bowel ≤12 weeks of study entry, symptomatic ascites/effusions requiring paracentesis or thoracentesis ≤30 days of study entry.
7. Known psychiatric disorder that would interfere with trial compliance.
8. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial.
9. Patient deprived of liberty, under guardianship, or under curatorship.

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
Experimental: Experimental arm; Densification of the chemotherapy administration dose and dosing schedule of carboplatin-paclitaxel (carboplatin AUC 5 every 3 weeks on day 1 and paclitaxel 80 mg/m2 every week, on day 1, day 8, and day 15, with 3 week-cycles) for 3 cycles +/- combined with daily sub-cutaneous administrations of GCSF 30 MUI days 3 to 5, & 10 to 12, & 17 to 19 (at investigator discretion, as per standard of care).	Drug: Carboplatin; Patients will be randomized 1:1: Experimental arm: Densification of the chemotherapy administration dose and dosing schedule of carboplatin-paclitaxel (carboplatin AUC 5 every 3 weeks on day 1 and paclitaxel 80 mg/m2 every week, on day 1, day 8, and day 15, with 3 week-cycles) for 3 cycles; Standard arm: Continuation of the same 3-weekly carboplatin-paclitaxel, as administered during the neo-adjuvant chemotherapy; Drug: Paclitaxel; Patients will be randomized 1:1: Experimental arm: Densification of the chemotherapy administration dose and dosing schedule of carboplatin-paclitaxel (carboplatin AUC 5 every 3 weeks on day 1 and paclitaxel 80 mg/m2 every week, on day 1, day 8, and day 15, with 3 week-cycles) for 3 cycles; Standard arm: Continuation of the same 3-weekly carboplatin-paclitaxel, as administered during the neo-adjuvant chemotherapy
Active Comparator: Standard; Continuation of the same 3-weekly carboplatin-paclitaxel, as administered during the neo-adjuvant chemotherapy +/- combined with peg-GCSF or GCSF daily sub-cutaneous administrations, at investigator discretion, as per standard of care.	Drug: Carboplatin; Patients will be randomized 1:1: Experimental arm: Densification of the chemotherapy administration dose and dosing schedule of carboplatin-paclitaxel (carboplatin AUC 5 every 3 weeks on day 1 and paclitaxel 80 mg/m2 every week, on day 1, day 8, and day 15, with 3 week-cycles) for 3 cycles; Standard arm: Continuation of the same 3-weekly carboplatin-paclitaxel, as administered during the neo-adjuvant chemotherapy; Drug: Paclitaxel; Patients will be randomized 1:1: Experimental arm: Densification of the chemotherapy administration dose and dosing schedule of carboplatin-paclitaxel (carboplatin AUC 5 every 3 weeks on day 1 and paclitaxel 80 mg/m2 every week, on day 1, day 8, and day 15, with 3 week-cycles) for 3 cycles; Standard arm: Continuation of the same 3-weekly carboplatin-paclitaxel, as administered during the neo-adjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients operated with late complete debulking surgery	To demonstrate the superiority in terms of efficacy of a densification of the chemotherapy with the salvage weekly dose-dense carboplatin-paclitaxel regimen compared to the continuation of the standard 3-weekly carboplatin-paclitaxel, in ovarian cancer patients found to have a poor prognostic disease (characterized by a poor chemosensitivity, with an unfavorable KELIMTM score < 1.0, and a disease not amenable to complete interval debulking surgery) after 3 cycles of standard neo-adjuvant chemotherapy.	From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days
Overall survival (OS)	To demonstrate the superiority in terms of efficacy of a densification of the chemotherapy with the salvage weekly dose-dense carboplatin-paclitaxel regimen compared to the continuation of the standard 3-weekly carboplatin-paclitaxel, in ovarian cancer patients found to have a poor prognostic disease (characterized by a poor chemosensitivity, with an unfavorable KELIMTM score < 1.0, and a disease not amenable to complete interval debulking surgery) after 3 cycles of standard neo-adjuvant chemotherapy.	From the date of randomization until death due to any cause, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients treated with a subsequent maintenance treatment with a PARP inhibitor (%) in the whole population	To assess the impact of the adjustment to the salvage weekly dose-dense regimen on the rate of subsequent prescription of PARP inhibitors (since these drugs are indicated in patients with complete or partial response to platinum-based chemotherapy) in terms of survival.	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
Progression-free survival and overall survival in these patients compared to those not treated with PARP inhibitor	To assess the impact of the adjustment to the salvage weekly dose-dense regimen on the rate of subsequent prescription of PARP inhibitors (since these drugs are indicated in patients with complete or partial response to platinum-based chemotherapy) in terms of survival.	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes In the population of patients treated with bevacizumab: - Overall response rate according to RECIST V1.1	To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
Adverse events graded according to the NCI Common Terminology Criteria Adverse Event Version 5.0	To compare the safety profiles of the salvage weekly dose-dense chemotherapy arm with those of the standard 3-weekly carboplatin-paclitaxel with/without bevacizumab, based on the observed adverse-events	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
To assess the impact of adding bevacizumab to chemotherapy on the efficacy outcomes In the population of patients treated with bevacizumab: - Progression-free survival & overall survival according to RECIST V1.1	To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
To assess the impact of adding bevacizumab to chemotherapy on the efficacy outcomes In the population of patients treated with bevacizumab: - Percentage of patients operated with a late complete debulking surgery (%)	To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
Percentage of patients operated with late complete debulking surgery, regardless of the number of chemotherapy cycles received	To compare the efficacy, in term of percentage of patients operated with late complete debulking surgery, between the salvage weekly dose-dense regimen and the standard regimen, regardless of the number of chemotherapy cycles received.	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
Overall response rate according to RECIST V1.1 in the whole population	To compare the efficacy of the salvage weekly dose-dense regimen with those of the standard regimen in terms of: Radiological response after 3 cycles of treatment, based on the best radiological response using RECIST criteria; Progression-free survival	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years
Progression-free survival in the whole population	To compare the efficacy of the salvage weekly dose-dense regimen with those of the standard regimen in terms of: • Radiological response after 3 cycles of treatment, based on the best radiological response using RECIST criteria	from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceptions of the patient-doctor relationship in patients offered bevacizumab/debulking surgery/PARPi	Measure of patient-doctor relationship: The Patient-Doctor Relationship Questionnaire measures patient perceptions of the patient-doctor relationship. Participants rate the level of helpfulness, time, trust, understanding, dedication, agreement, availability, contentment, and accessibility of their healthcare provider. All nine items are rated on a five-point Likert scale from 1 (Not at all appropriate) to 5 (totally appropriate). Mean scores are calculated, and higher scores indicate a better perceived doctor-patient relationship.	From 4-8 weeks after a decision on bevacizumab (approx. at randomization date) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Satisfaction with decision-making process in patients offered bevacizumab/debulking surgery/PARPi	Measure of satisfaction with care: One self-generated item developed on the basis of the literature will ask patients in general how they would rate the care they received for their ovarian cancer treatment during the past three months, using a five-point scale from 1 (poor) to 5 (excellent). A higher score reflects a higher satisfaction with their care.	From 4-8 weeks after a decision on bevacizumab (approx. at randomization date) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Satisfaction with decision-making process in patients offered bevacizumab/debulking surgery/PARPi	Measure of decision satisfaction: The Satisfaction with Decision scale measures a patient's level of satisfaction with healthcare decisions. It consists of six statements to which respondents are asked to indicate their level of agreement using a five-point scale, from 1 (strongly disagree) to 5 (strongly agree). Total scores are summed, with higher scores indicating greater decisional satisfaction.	From 4-8 weeks after a decision on bevacizumab (approx. at randomization date) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Emotional wellbeing following the decision-making process in patients offered bevacizumab/debulking surgery/PARPi	To determine the impact of the decision-making process on emotional wellbeing in the short- and medium-term, among patients who have participated in decision-making regarding bevacizumab as a chemosensitizer, late debulking surgery in the case of favorable response to chemotherapy, or PARP inhibitors and/or bevacizumab as maintenance treatment. Measure of emotional wellbeing: Six self-generated items will be used to measure the concept of eudaimonic or hedonic wellbeing. A 10-point scale from 1 (not at all) to 10 (very much so) will gauge perceptions of feeling hopeful, peaceful, grateful, comforted, connected, and content over the past week, presented as single-word descriptors. Mean scores will be calculated for each subscale, and a mean across all items will be derived to reflect overall emotional wellbeing. Higher scores indicate higher levels of emotional wellbeing.	From 4-8 weeks after a decision on bevacizumab (approx. at randomization date) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Treatment beliefs in patients offered bevacizumab/PARPi	Measure of treatment beliefs: For patients prescribed PARP inhibitors and/or bevacizumab, four items will be presented to measure treatment beliefs in relation to these treatments. These items are adapted from a Treatment Beliefs Questionnaire originally developed for patients with low back pain, which has been adapted for the current setting with permission. This self-report scale consists of four items assessing perceptions of credibility, effectiveness, concerns, and individual fit of treatment, which are rated on a five-point scale from (1) strongly disagree to (5) strongly agree. Higher scores for each item indicate more positive beliefs about the treatment (with responses on the 'concerns' item being reverse scored).	From 4-8 weeks after a decision on bevacizumab (approx. at randomization date) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Self-reported adherence to PARPi in patients offered PARPi	Measure of treatment (PARPi) adherence: For patients prescribed PARP inhibitors, a three-item scale will be used to measure adherence to PARPi and bevacizumab. Patients will be asked about the number of days in which they missed at least one dose of the treatment (answered numerically), the frequency with which they took their medication in the way they were supposed to over the previous 30 days (rated on a 6-point scale from never to always), and their rating of how 'good a job' they did at taking their medication in the way recommended over the previous 30 days (rated on a 6-point scale from very poor to excellent). Responses will be linearly transformed to a 0-100 scale for analyses, with 0 representing the worst adherence and 100 the best. Summary scores will be calculated as the mean of the three items.	From 4-8 weeks after a decision on PARPi (approx. at end of chemotherapy) through end of follow-up (2-3 years after inclusion, depending on debulking surgery)
Percentage of patients with BRCA (BReast CAncer) mutation (%)	Number of patients with BRCA mutation involved in homologous recombination (%)	from date of randomization through study completion, an average of 5 years
Percentage of patients with BRCA wild-type HRD (Homologous Recombination Deficiency) disease (%)	Number of patients with BRCA wild-type HRD mutation involved in homologous recombination (%)	from date of randomization until end of study, for a period of 5 years
Percentage of patients with BRCA wild-type HRP (Homologous Recombination Proficient) disease (%)	Number of patients with BRCA wild-type HRP mutation involved in homologous recombination (%)	from date of randomization through study completion, an average of 3 years
Tests/assays used (names, proprietary)	Name of tests/assays used in real-life setting	from date of randomization until end of study, through study completion, an average of 3 years
Percentage of tests/assays used (names, proprietary) (%)	Percentage of tests/assays used in real-life setting (%)	from date of randomization until end of study, through study completion, an average of 3 years
Incremental cost-effectiveness ratio	To assess the cost-effectiveness evaluations of the experimental treatment (medico-economic evaluation) in the French context Salvage weekly dose-dense regimen vs the standard 3-weekly regimen, as per randomization Addition of bevacizumab to chemotherapy, as per investigator decision Late debulking surgery after chemotherapy in the case of favorable response to chemotherapy, as per investigator decision Maintenance treatment with bevacizumab with/without PARP inhibitor, or surveillance, as per investigator decision	from date of randomization until end of study, for a period of 5 years
Estimate the net financial impact over 5 years	A budget impact analysis (BIA) to estimate the financial impact for French Health Insurance of the generalization in the French context of the strategy based on the experimental treatment.	from date of randomization until end of study, for a period of 5 years
Quality of life questionnaires	To compare the quality of life and patient-reported outcomes of the salvage chemotherapy arm with those of the standard regimen	from date of randomization through study completion, an average of 3 years
Incremental cost-utility ratio	To assess the cost-utility evaluations of the experimental treatment (medico-economic evaluation) in the French context Salvage weekly dose-dense regimen vs the standard regimen, as per randomization Addition of bevacizumab to chemotherapy, as per investigator decision Late debulking surgery after chemotherapy in the case of favorable response to chemotherapy, as per investigator decision Maintenance treatment with bevacizumab with/without PARP inhibitor, or surveillance, as per investigator decision	from date of randomization until end of study, for a periof of 5 years

Collaborators and Investigators

• Sponsor: ARCAGY/ GINECO GROUP
• Collaborators: Horizon 2020 - European Commission
• Investigators: Principal Investigator: Benoit YOU, HCL - Centre Hospitalier Lyon Sud

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; poor prognostic; unfavorable primary chemosensitivity; incomplete debulking surgery; KELIM
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel
• Other Study ID Numbers: 2023-508260-30-01; RECF-005636 (Other Identifier: INCA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No