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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 · ARCAGY/ GINECO GROUP
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Official title
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
About this study
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.
Eligibility criteria
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 Non-inclusion 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 during the randomized chemotherapy phase for both arms. 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 design
Enrollment target: 250 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-07-30
Estimated completion: 2028-06
Last updated: 2026-08-04
Interventions
Drug: CarboplatinDrug: Paclitaxel
Primary outcomes
  • Percentage of patients operated with late complete debulking surgery (From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days)
  • Overall survival (OS) (From the date of randomization until death due to any cause, assessed up to 5 years)
Sponsor
ARCAGY/ GINECO GROUP · other
With: Horizon 2020 - European Commission
Contacts & investigators
ContactMarine COGNAT · contact · salvovar.trial@arcagy.org · +33 1 84 85 20 20
InvestigatorBenoit YOU · principal_investigator, HCL - Centre Hospitalier Lyon Sud
All locations (76)
ICO Paul PapinRecruiting
Angers, France
CH d'AvignonRecruiting
Avignon, France
Sainte-Catherine Institut du Cancer Avignon-ProvenceRecruiting
Avignon, France
Hôpital de la Côte BasqueRecruiting
Bayonne, France
CHRU Besançon - Hôpital Jean MinjozRecruiting
Besançon, France
Institut BergoniéRecruiting
Bordeaux, France
CHU de BREST - Hôpital Cavale BlancheRecruiting
Brest, France
Centre François BaclesseRecruiting
Caen, France
Centre d'Oncologie et de Radiothérapie 37 (ROC37)Recruiting
Chambray-lès-Tours, France
Centre Hospitalier de CholetRecruiting
Cholet, France
Centre Jean PerrinRecruiting
Clermont-Ferrand, France
Centre Hospitalier Alpes LemanNot Yet Recruiting
Contamine-sur-Arve, France
Centre Hospitalier Intercommunal de CréteilRecruiting
Créteil, France
Centre Georges François LeclercRecruiting
Dijon, France
CHU de DijonRecruiting
Dijon, France
Groupe Hospitalier Mutualiste de GrenobleRecruiting
Grenoble, France
Hôpital André MignotRecruiting
Le Chesnay, France
CHRU de LilleNot Yet Recruiting
Lille, France
Centre Oscar LambretRecruiting
Lille, France
CHU de Limoges - Hôpital DupuytrenRecruiting
Limoges, France
Hôpital de la Croix RousseNot Yet Recruiting
Lyon, France
Centre Léon BérardRecruiting
Lyon, France
Hôpital Privé Jean MermozRecruiting
Lyon, France
Hôpital de la TimoneNot Yet Recruiting
Marseille, France
CHRU de Montpellier - Hôpital Saint-EloiRecruiting
Montpellier, France
ICM Val d'AurelleRecruiting
Montpellier, France
Centre Azuréen de CancérologieRecruiting
Mougins, France
Hôpital Privé du ConfluentRecruiting
Nantes, France
Centre Antoine LacassagneRecruiting
Nice, France
Institut de Cancérologie du Gard - CHU de NîmesRecruiting
Nîmes, France
Groupe Hospitalier Diaconesses - Croix Saint-SimonRecruiting
Paris, France
Hôpital CochinRecruiting
Paris, France
Hôpital Européen George PompidouRecruiting
Paris, France
Institut CurieRecruiting
Paris, France
Centre Hospitalier Général de PauRecruiting
Pau, France
HCL - Centre Hospitalier Lyon SudRecruiting
Pierre-Bénite, France
Hôpital de Poissy-Saint-Germain-en-LayeNot Yet Recruiting
Poissy, France
Institut Jean GodinotRecruiting
Reims, France
Centre Eugène MarquisRecruiting
Rennes, France
Hôpital Privé de la LoireNot Yet Recruiting
Saint-Etienne, France
Institut de Cancérologie de l'Ouest - ICORecruiting
Saint-Herblain, France
CHU Saint-Etienne - Pôle de CancérologieRecruiting
Saint-Priest-en-Jarez, France
ICANS - Institut de cancérologie Strasbourg EuropeRecruiting
Strasbourg, France
CHU Strasbourg - Hôpital de HautepierreRecruiting
Strasbourg, France
Hôpital FochRecruiting
Suresnes, France
Hôpitaux du Léman - site Thonon-les-BainsNot Yet Recruiting
Thonon-les-Bains, France
Oncopole Claudius Régaud - IUCT OncopoleRecruiting
Toulouse, France
Clinique PasteurRecruiting
Toulouse, France
Centre Hospitalier de ValenceRecruiting
Valence, France
Gustave RoussyRecruiting
Villejuif, France
Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo AlessandriaNot Yet Recruiting
Alessandria, Italy
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere ScientificoRecruiting
Bologna, Italy
Careggi University HospitalNot Yet Recruiting
Florence, Italy
Alessandro Manzoni HospitalNot Yet Recruiting
Lecco, Italy
Istituto Europeo Di Oncologia S.r.l.Recruiting
Milan, Italy
Azienda Ulss 3 SerenissimaNot Yet Recruiting
Venice, Italy
The University of Tokyo HospitalNot Yet Recruiting
Bunkyō City, Japan
Fukushima Medical University HospitalRecruiting
Fukushima, Japan
Saitama Medical University International Medical CenterRecruiting
Hidaka, Japan
Hirosaki University HospitalNot Yet Recruiting
Hirosaki, Japan
The Jikei University Kashiwa HospitalRecruiting
Kashiwa, Japan
St. Marianna University HospitalRecruiting
Kawasaki, Japan
Dokkyo Medical University Saitama Medical CenterNot Yet Recruiting
Koshigaya, Japan
Kurume University HospitalNot Yet Recruiting
Kurume, Japan
Nagoya University HospitalRecruiting
Nagoya, Japan
Kindai University HospitalRecruiting
Sayama, Japan
Tohoku University HospitalRecruiting
Sendai, Japan
Osaka Medical and Pharmaceutical University HospitalNot Yet Recruiting
Takatsuki, Japan
The Cancer Institute Hospital Of JFCRNot Yet Recruiting
Tokyo, Japan
The Jikei University Daisan HospitalNot Yet Recruiting
Tokyo, Japan
The Jikei University HospitalRecruiting
Tokyo, Japan
The Jikei University Katsushika Medical CenterNot Yet Recruiting
Tokyo, Japan
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis StichtingNot Yet Recruiting
Amsterdam, Netherlands
Leids Universitair Medisch Centrum (LUMC)Not Yet Recruiting
Leiden, Netherlands
Radboud University Medical CenterNot Yet Recruiting
Nijmegen, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)Not Yet Recruiting
Rotterdam, Netherlands
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 · TrialPath