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
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
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
Study 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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
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 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.
Overall survival (OS) — From the date of randomization until death due to any cause, assessed up to 5 years 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.
Trial sites (76)
Facility
City
Region
Status
ICO Paul Papin
Angers
France
Recruiting
CH d'Avignon
Avignon
France
Recruiting
Sainte-Catherine Institut du Cancer Avignon-Provence
Avignon
France
Recruiting
Hôpital de la Côte Basque
Bayonne
France
Recruiting
CHRU Besançon - Hôpital Jean Minjoz
Besançon
France
Recruiting
Institut Bergonié
Bordeaux
France
Recruiting
CHU de BREST - Hôpital Cavale Blanche
Brest
France
Recruiting
Centre François Baclesse
Caen
France
Recruiting
Centre d'Oncologie et de Radiothérapie 37 (ROC37)
Chambray-lès-Tours
France
Recruiting
Centre Hospitalier de Cholet
Cholet
France
Recruiting
Centre Jean Perrin
Clermont-Ferrand
France
Recruiting
Centre Hospitalier Alpes Leman
Contamine-sur-Arve
France
Not Yet Recruiting
Centre Hospitalier Intercommunal de Créteil
Créteil
France
Recruiting
Centre Georges François Leclerc
Dijon
France
Recruiting
CHU de Dijon
Dijon
France
Recruiting
Groupe Hospitalier Mutualiste de Grenoble
Grenoble
France
Recruiting
Hôpital André Mignot
Le Chesnay
France
Recruiting
CHRU de Lille
Lille
France
Not Yet Recruiting
Centre Oscar Lambret
Lille
France
Recruiting
CHU de Limoges - Hôpital Dupuytren
Limoges
France
Recruiting
Hôpital de la Croix Rousse
Lyon
France
Not Yet Recruiting
Centre Léon Bérard
Lyon
France
Recruiting
Hôpital Privé Jean Mermoz
Lyon
France
Recruiting
Hôpital de la Timone
Marseille
France
Not Yet Recruiting
CHRU de Montpellier - Hôpital Saint-Eloi
Montpellier
France
Recruiting
ICM Val d'Aurelle
Montpellier
France
Recruiting
Centre Azuréen de Cancérologie
Mougins
France
Recruiting
Hôpital Privé du Confluent
Nantes
France
Recruiting
Centre Antoine Lacassagne
Nice
France
Recruiting
Institut de Cancérologie du Gard - CHU de Nîmes
Nîmes
France
Recruiting
Groupe Hospitalier Diaconesses - Croix Saint-Simon
Paris
France
Recruiting
Hôpital Cochin
Paris
France
Recruiting
Hôpital Européen George Pompidou
Paris
France
Recruiting
Institut Curie
Paris
France
Recruiting
Centre Hospitalier Général de Pau
Pau
France
Recruiting
HCL - Centre Hospitalier Lyon Sud
Pierre-Bénite
France
Recruiting
Hôpital de Poissy-Saint-Germain-en-Laye
Poissy
France
Not Yet Recruiting
Institut Jean Godinot
Reims
France
Recruiting
Centre Eugène Marquis
Rennes
France
Recruiting
Hôpital Privé de la Loire
Saint-Etienne
France
Not Yet Recruiting
+ 36 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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