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

NCT06476184 | Recruiting Phase 3 DMC

• 2 other identifiers: 2023-508260-30-01RECF-005636
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 72

Brief 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.

Conditions

Ovarian Cancer

Keywords

chemotherapy; poor prognostic; unfavorable primary chemosensitivity; incomplete debulking surgery; KELIM

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Percentage of patients operated with late complete debulking surgery, 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

  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

  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

  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

  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 Outcomes (15)

• Quality of life questionnaires

  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

  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

  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)

Study Arms (2)

Experimental arm

EXPERIMENTAL

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; Drug: Paclitaxel

Standard

ACTIVE COMPARATOR

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; Drug: Paclitaxel

Interventions

Carboplatin DRUG

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

Experimental arm; Standard

Paclitaxel DRUG

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

Experimental arm; Standard

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed high-grade epithelial (serous, endometrioid, or carcinosarcoma with a ≥30% epithelial tumor component) ovarian, primary peritoneal, or fallopian-tube carcinoma
• Adult patient aged ≥ 18 years old
• Advanced stage III or IV disease
• 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)
• ECOG performance status 0 or 1 (see appendix 2)
• 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),
• 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)
• Patients who gave its written informed consent to participate to the study
• Patients affiliated to a social insurance regime
• 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

You may not qualify if:

• 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)
• Previous treatment with bevacizumab during initial standard neo-adjuvant chemotherapy
• Has primary platinum-refractory disease, defined as disease that has progressed during the neo-adjuvant chemotherapy
• 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
• Treatment with other investigational agents in clinical trials.
• 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.
• Known psychiatric disorder that would interfere with trial compliance.
• Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial.
• Patient deprived of liberty, under guardianship, or under curatorship.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• Horizon 2020 - European Commission: collaborator

Study Sites (72)

ICO Paul Papin

Angers, 49055, France

RECRUITING

CH d'Avignon

Avignon, 84902, France

RECRUITING

Sainte-Catherine Institut du Cancer Avignon-Provence

Avignon, 84918, France

RECRUITING

Hôpital de la Côte Basque

Bayonne, 64100, France

RECRUITING

CHRU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

RECRUITING

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

CHU de BREST - Hôpital Cavale Blanche

Brest, 29200, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

RECRUITING

Centre d'Oncologie et de Radiothérapie 37 (ROC37)

Chambray-lès-Tours, 37170, France

RECRUITING

Centre Hospitalier de Cholet

Cholet, 49300, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Centre Hospitalier Alpes Leman

Contamine-sur-Arve, 74130, France

NOT YET RECRUITING

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

CHU de Dijon

Dijon, 21079, France

RECRUITING

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38028, France

RECRUITING

Hôpital André Mignot

Le Chesnay, 78157, France

NOT YET RECRUITING

CHRU de Lille

Lille, 59000, France

NOT YET RECRUITING

Centre Oscar Lambret

Lille, 59020, France

NOT YET RECRUITING

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

RECRUITING

Hôpital de la Croix Rousse

Lyon, 69229, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Hôpital Privé Jean Mermoz

Lyon, 69373, France

RECRUITING

Hôpital de la Timone

Marseille, 13005, France

NOT YET RECRUITING

CHRU de Montpellier - Hôpital Saint-Eloi

Montpellier, 34059, France

NOT YET RECRUITING

ICM Val d'Aurelle

Montpellier, 34298, France

NOT YET RECRUITING

Centre Azuréen de Cancérologie

Mougins, 06250, France

RECRUITING

Hôpital Privé du Confluent

Nantes, 44202, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Institut de Cancérologie du Gard - CHU de Nîmes

Nîmes, 30029, France

RECRUITING

Groupe Hospitalier Diaconesses - Croix Saint-Simon

Paris, 75012, France

RECRUITING

Hôpital Cochin

Paris, 75014, France

RECRUITING

Hôpital Européen George Pompidou

Paris, 75015, France

NOT YET RECRUITING

Institut Curie

Paris, 75248, France

RECRUITING

Centre Hospitalier Général de Pau

Pau, 64046, France

RECRUITING

HCL - Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

RECRUITING

Hôpital de Poissy-Saint-Germain-en-Laye

Poissy, 78303, France

NOT YET RECRUITING

Institut Jean Godinot

Reims, 51056, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

RECRUITING

Hôpital Privé de la Loire

Saint-Etienne, 42100, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest - ICO

Saint-Herblain, 44805, France

RECRUITING

CHU Saint-Etienne - Pôle de Cancérologie

Saint-Priest-en-Jarez, 42271, France

RECRUITING

ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, 67033, France

RECRUITING

CHU Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098, France

NOT YET RECRUITING

Hôpital Foch

Suresnes, 92151, France

RECRUITING

Hôpitaux du Léman - site Thonon-les-Bains

Thonon-les-Bains, 74203, France

NOT YET RECRUITING

Oncopole Claudius Régaud - IUCT Oncopole

Toulouse, 31059, France

RECRUITING

Clinique Pasteur

Toulouse, 31300, France

RECRUITING

Centre Hospitalier de Valence

Valence, 26953, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria

Alessandria, 15121, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Bologna, 40138, Italy

NOT YET RECRUITING

Careggi University Hospital

Florence, 50134, Italy

NOT YET RECRUITING

Alessandro Manzoni Hospital

Lecco, 23900, Italy

NOT YET RECRUITING

Istituto Europeo Di Oncologia S.r.l.

Milan, 20141, Italy

NOT YET RECRUITING

Azienda Ulss 3 Serenissima

Venice, 30174, Italy

NOT YET RECRUITING

The University of Tokyo Hospital

Bunkyō City, Japan

NOT YET RECRUITING

Fukushima Medical University Hospital

Fukushima, Japan

NOT YET RECRUITING

Saitama Medical University International Medical Center

Hidaka, Japan

RECRUITING

Hirosaki University Hospital

Hirosaki, Japan

NOT YET RECRUITING

The Jikei University Kashiwa Hospital

Kashiwa, Japan

NOT YET RECRUITING

St. Marianna University Hospital

Kawasaki, Japan

NOT YET RECRUITING

Dokkyo Medical University Saitama Medical Center

Koshigaya, Japan

NOT YET RECRUITING

Kurume University Hospital

Kurume, Japan

NOT YET RECRUITING

Nagoya University Hospital

Nagoya, Japan

NOT YET RECRUITING

Kindai University Hospital

Sayama, Japan

NOT YET RECRUITING

Tohoku University Hospital

Sendai, Japan

NOT YET RECRUITING

Osaka Medical and Pharmaceutical University Hospital

Takatsuki, Japan

NOT YET RECRUITING

The Cancer Institute Hospital Of JFCR

Tokyo, Japan

NOT YET RECRUITING

The Jikei University Daisan Hospital

Tokyo, Japan

NOT YET RECRUITING

The Jikei University Hospital

Tokyo, Japan

NOT YET RECRUITING

The Jikei University Katsushika Medical Center

Tokyo, Japan

NOT YET RECRUITING

Related Publications (1)

• Chator C, Yanaihara N, Chabaud S, Parma GM, Dima AL, Clamp A, Ferron G, Kroep JR, Leary A, Cibula D, Fiteni F, Bruchim I, Serrier H, Carroll S, Belmont AS, Peron J, You B. SALVOVAR: a pragmatic randomized phase III trial comparing the SALVage weekly dose-dense regimen to the standard 3-weekly regimen in patients with poor prognostic OVARian cancers. Ther Adv Med Oncol. 2025 Dec 23;17:17588359251396777. doi: 10.1177/17588359251396777. eCollection 2025.

  PMID: 41466844 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Benoit YOU

  HCL - Centre Hospitalier Lyon Sud

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marine COGNAT

CONTACT

+33 1 84 85 20 20; salvovar.trial@arcagy.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 +/- combined with daily sub-cutaneous administrations of GCSF (Granulocyte Colony-Stimulating Factor) 30 MUI days 3 to 5, \& 10 to 12, \& 17 to 19 (at investigator discretion, as per standard of care) * Standard arm: 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. Of note, bevacizumab addition in both arms is required in countries where it is available as per standard of care, according to country health coverage policy.

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 26, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-11

Locations

FR (50); JP (16); IT (6)