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
NCT Number: NCT06476184
Acronym: SALVOVAR
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Ovarian Cancer
Interventions: DRUG: Carboplatin|DRUG: Paclitaxel
Sponsor: ARCAGY/ GINECO GROUP
Collaborators: Horizon 2020 - European Commission
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 250
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-05
Completion Date: 2028-06
Locations: ICO Paul Papin, Angers, 49055, France|Sainte-Catherine Institut du Cancer Avignon-Provence, Avignon, 84918, France|Hôpital de la Côte Basque, Bayonne, 64100, France|CHRU Besançon - Hôpital Jean Minjoz, Besançon, 25030, France|Institut Bergonié, Bordeaux, 33076, France|CHU de BREST - Hôpital Cavale Blanche, Brest, 29200, France|Centre François Baclesse, Caen, 14076, France|Centre d'Oncologie et de Radiothérapie 37 (ROC37), Chambray-lès-Tours, 37170, France|Centre Jean Perrin, Clermont-ferrand, 63011, France|Centre Hospitalier Alpes Leman, Contamine-sur-arve, 74130, France|Centre Hospitalier Intercommunal de Créteil, Créteil, 94010, France|CHU de Dijon, Dijon, 21079, France|Groupe Hospitalier Mutualiste de Grenoble, Grenoble, 38028, France|Hôpital André Mignot, Le Chesnay, 78157, France|CHU de Limoges - Hôpital Dupuytren, Limoges, 87042, France|Centre Léon Bérard, Lyon, 69373, France|Hôpital Privé Jean Mermoz, Lyon, 69373, France|ICM Val d'Aurelle, Montpellier, 34298, France|Centre Azuréen de Cancérologie, Mougins, 06250, France|Hôpital Privé du Confluent, Nantes, 44202, France|Centre Antoine Lacassagne, Nice, 06189, France|Institut de Cancérologie du Gard - CHU de Nîmes, Nîmes, 30029, France|Groupe Hospitalier Diaconesses - Croix Saint-Simon, Paris, 75012, France|Hôpital Cochin, Paris, 75014, France|Institut Curie, Paris, 75248, France|Centre Hospitalier Général de Pau, Pau, 64046, France|HCL - Centre Hospitalier Lyon Sud, Pierre-Bénite, 69495, France|Centre CARIO - HPCA, Plérin, 22190, France|Centre Eugène Marquis, Rennes, 35042, France|Institut de Cancérologie de l'Ouest - ICO, Saint-Herblain, 44805, France|ICANS - Institut de cancérologie Strasbourg Europe, Strasbourg, 67033, France|IUCT Oncopole - Institut Claudius Régaud, Toulouse, 31059, France|Clinique Pasteur, Toulouse, 31300, France|Centre Hospitalier de Valence, Valence, 26953, France|Gustave Roussy, Villejuif, 94805, France

Summary:
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.

Primary Outcome Measures: 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 to 4 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 to 4 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: 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 3-weekly carboplatin-paclitaxel 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 3-weekly carboplatin-paclitaxel 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|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
Other Outcome Measures: Quality of life questionnaires, To compare the quality of life and patient-reported outcomes of the salvage chemotherapy arm with those of the standard 3-weekly carboplatin-paclitaxel, from date of randomization through study completion, an average of 3 years|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-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 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 periof of 5 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