Trial Title:
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 ID:
NCT06476184
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Carboplatin
Conditions: Keywords:
chemotherapy
poor prognostic
unfavorable primary chemosensitivity
incomplete debulking surgery
KELIM
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
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
Arm group label:
Experimental arm
Arm group label:
Standard
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
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
Arm group label:
Experimental arm
Arm group label:
Standard
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.
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.
Criteria for 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 KELIM 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) or 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. No 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.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ICO Paul Papin
Address:
City:
Angers
Zip:
49055
Country:
France
Status:
Recruiting
Contact:
Last name:
Sophie ABADIE-LACOURTOISIE
Facility:
Name:
Sainte-Catherine Institut du Cancer Avignon-Provence
Address:
City:
Avignon
Zip:
84918
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Julien GRENIER
Facility:
Name:
Hôpital de la Côte Basque
Address:
City:
Bayonne
Zip:
64100
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Thomas GRELLETY
Facility:
Name:
CHRU Besançon - Hôpital Jean Minjoz
Address:
City:
Besançon
Zip:
25030
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laura MANSI
Facility:
Name:
Institut Bergonié
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Coriolan LEBRETON
Facility:
Name:
CHU de BREST - Hôpital Cavale Blanche
Address:
City:
Brest
Zip:
29200
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laura DEIANA
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Zip:
14076
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Florence JOLY
Facility:
Name:
Centre d'Oncologie et de Radiothérapie 37 (ROC37)
Address:
City:
Chambray-lès-Tours
Zip:
37170
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Pierre COMBE
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-ferrand
Zip:
63011
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laure VACHER
Facility:
Name:
Centre Hospitalier Alpes Leman
Address:
City:
Contamine-sur-arve
Zip:
74130
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Mansour RASTKHAH
Facility:
Name:
Centre Hospitalier Intercommunal de Créteil
Address:
City:
Créteil
Zip:
94010
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Zineb SELLAM-CHORFI
Facility:
Name:
CHU de Dijon
Address:
City:
Dijon
Zip:
21079
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Marie CHAIX
Facility:
Name:
Groupe Hospitalier Mutualiste de Grenoble
Address:
City:
Grenoble
Zip:
38028
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Elise BONNET
Facility:
Name:
Hôpital André Mignot
Address:
City:
Le Chesnay
Zip:
78157
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sophie BARTHIER
Facility:
Name:
CHU de Limoges - Hôpital Dupuytren
Address:
City:
Limoges
Zip:
87042
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laurence VENAT-BOUVET
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69373
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Philippe TOUSSAINT
Facility:
Name:
Hôpital Privé Jean Mermoz
Address:
City:
Lyon
Zip:
69373
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Olfa DERBEL MILED
Facility:
Name:
ICM Val d'Aurelle
Address:
City:
Montpellier
Zip:
34298
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Michel FABBRO
Facility:
Name:
Centre Azuréen de Cancérologie
Address:
City:
Mougins
Zip:
06250
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Rémy LARGILLIER
Facility:
Name:
Hôpital Privé du Confluent
Address:
City:
Nantes
Zip:
44202
Country:
France
Status:
Recruiting
Contact:
Last name:
Cyriac BLONZ
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Zip:
06189
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Philippe FOLLANA
Facility:
Name:
Institut de Cancérologie du Gard - CHU de Nîmes
Address:
City:
Nîmes
Zip:
30029
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Frédéric FITENI
Facility:
Name:
Groupe Hospitalier Diaconesses - Croix Saint-Simon
Address:
City:
Paris
Zip:
75012
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Frédéric SELLE
Facility:
Name:
Hôpital Cochin
Address:
City:
Paris
Zip:
75014
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sixtine DE PERCIN
Facility:
Name:
Institut Curie
Address:
City:
Paris
Zip:
75248
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Manuel RODRIGUES
Facility:
Name:
Centre Hospitalier Général de Pau
Address:
City:
Pau
Zip:
64046
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Kevin BOURCIER
Facility:
Name:
HCL - Centre Hospitalier Lyon Sud
Address:
City:
Pierre-Bénite
Zip:
69495
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Benoit YOU
Facility:
Name:
Centre CARIO - HPCA
Address:
City:
Plérin
Zip:
22190
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Anne-Claire HARDY-BESSARD
Facility:
Name:
Centre Eugène Marquis
Address:
City:
Rennes
Zip:
35042
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Thibault DE LA MOTTE ROUGE
Facility:
Name:
Institut de Cancérologie de l'Ouest - ICO
Address:
City:
Saint-Herblain
Zip:
44805
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Dominique BERTON
Facility:
Name:
ICANS - Institut de cancérologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67033
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Lauriane EBERST
Facility:
Name:
IUCT Oncopole - Institut Claudius Régaud
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Gwénaël FERRON
Facility:
Name:
Clinique Pasteur
Address:
City:
Toulouse
Zip:
31300
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Mathilde MARTINEZ
Facility:
Name:
Centre Hospitalier de Valence
Address:
City:
Valence
Zip:
26953
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Rim BATTI
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Alexandra LEARY
Start date:
August 5, 2024
Completion date:
June 2028
Lead sponsor:
Agency:
ARCAGY/ GINECO GROUP
Agency class:
Other
Collaborator:
Agency:
Horizon 2020 - European Commission
Agency class:
Other
Source:
ARCAGY/ GINECO GROUP
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06476184
