CARBOPLATIN for Ovarian epithelial cancer | Ovarian cancer stage III | Ovarian cancer stage IV | Fallopian tube cancer stage III | Fallopian tube cancer stage IV | Primary peritoneal carcinosarcoma

Inclusion criteria

• {"criterion_text":"- 1. Histologically confirmed high-grade epithelial (serous, endometrioid, or carcinosarcoma with a ≥30% epithelial tumor component) ovarian, primary peritoneal, or fallopian-tube carcinoma\n- 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\n- 2. Adult patient aged ≥ 18 years old\n- 3. Advanced stage III or IV disease\n- 4. Treated with 3 to 4 neo-adjuvant cycles of standard 3-weekly carboplatin-paclitaxel regimen in first-line setting, and characterized by: o 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) o 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) GINECO-OV130b/ENGOT-ov78– SALVOVAR – Protocol - Version 1.0 – 14/DEC/2023 (From FORM 113-04: Protocol – Application date: 30/SEP/2022) Page 8 on 108 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\n- 5. ECOG performance status 0 or 1 (see appendix 2)\n- 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),\n- 7. Adequate renal and liver functions o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN in context of liver metastases o Total bilirubin ≤1.5 × ULN (patients with Gilbert’s are eligible if total bilirubin ≤3 × ULN) o Albumin ≥3 g/dL o 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)\n- 8. Patients who gave its written informed consent to participate to the study\n- 9. Patients affiliated to a social insurance regime"}

Exclusion criteria

• {"criterion_text":"- 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 (carboplatine, paclitaxel, GCSF)\n- 2. Previous treatment with bevacizumab during initial standard neo-adjuvant chemotherapy\n- 3. Has primary platinum-refractory disease, defined as disease that has progressed during the neo-adjuvant chemotherapy\n- 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\n- 5. Treatment with other investigational agents in clinical trials.\n- 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. GINECO-OV130b/ENGOT-ov78– SALVOVAR – Protocol - Version 1.0 – 14/DEC/2023 (From FORM 113-04: Protocol – Application date: 30/SEP/2022) Page 9 on 108 • 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.\n- 7. Known psychiatric disorder that would interfere with trial compliance.\n- 8. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial."}

Primary endpoints

• {"endpoint_text":"- - Percentage of patients operated with late complete debulking surgery after receiving 3 additional cycles of randomized chemotherapy (expected increase from 5% in the control arm to 20%)% in the experimental arm)","definition_or_measurement_approach":"Proportion of patients who undergo late complete debulking surgery after receiving 3 additional cycles of randomized chemotherapy; comparison of percentages between arms (control vs experimental)."}
• {"endpoint_text":"- - Overall survival improvement by 49% (HR = 0.61) in the whole population translating in an improvement in median OS from 20 months (control arm) to 32.8 months (experimental arm) with a 1:1 randomization","definition_or_measurement_approach":"Overall survival (OS) measured from randomization to death from any cause; hazard ratio and median OS used for comparison (target HR=0.61, median OS improvement from 20 to 32.8 months)."}

Secondary endpoints

• {"endpoint_text":"- - Overall response rate according to RECIST V1.1 in the whole population (see appendix 4)","definition_or_measurement_approach":"Radiological response assessed using RECIST v1.1; best overall response."}
• {"endpoint_text":"- - Progression-free survival in the whole population","definition_or_measurement_approach":"Time from randomization to disease progression or death (PFS)."}
• {"endpoint_text":"- - Percentage of patients treated with a subsequent maintenance treatment with a PARP inhibitor (%) in the whole population","definition_or_measurement_approach":"Proportion of patients receiving PARP inhibitor maintenance after study treatment."}
• {"endpoint_text":"- - Progression-free survival and overall survival in these patients compared to those not treated with PARP inhibitor","definition_or_measurement_approach":"PFS and OS comparisons between patients who received PARP inhibitor maintenance versus those who did not."}
• {"endpoint_text":"- - In the population of patients treated with bevacizumab: • Overall response rate according to RECIST V1.1 • Progression-free survival & overall survival according to RECIST V1.1 • Percentage of patients operated with a late complete debulking surgery (%)","definition_or_measurement_approach":"Subgroup analyses for patients receiving bevacizumab: RECIST v1.1 response rates, PFS and OS, and rate of late complete debulking surgery."}
• {"endpoint_text":"- - Adverse events graded according to the NCI Common Terminology Criteria Adverse Event Version 5.0 (see appendix 3)","definition_or_measurement_approach":"Safety assessed by recording adverse events and grading per NCI CTCAE v5.0."}
• {"endpoint_text":"- - Quality of life questionnaires","definition_or_measurement_approach":"Patient-reported quality of life assessed using questionnaires (e.g., QLQ-OV28, QLQ-C30 as indicated in documents)."}
• {"endpoint_text":"- - To determine the impact of patient beliefs, preferences and experiences on the decision-making process; endpoint: shared decision-making","definition_or_measurement_approach":"Assessment of shared decision-making through questionnaires and related measures."}
• {"endpoint_text":"- - To determine the impact of the shared decision-making process on outcomes in the short- and medium-term; endpoints: satisfaction with care, satisfaction with decision, patient-doctor relationship, emotions, treatment beliefs, treatment adherence, and quality of life.","definition_or_measurement_approach":"Patient-reported outcomes and measures of satisfaction, relationship, emotions, beliefs, adherence, and QoL over short- and medium-term follow-up."}
• {"endpoint_text":"- - Percentage of patients with BRCA mutation (%)","definition_or_measurement_approach":"Proportion of patients with BRCA mutation based on tumor/germline testing."}
• {"endpoint_text":"- - Percentage of patients with BRCA wild-type HRD disease (%)","definition_or_measurement_approach":"Proportion of patients with BRCA wild-type HRD disease as defined by genomic instability scoring."}
• {"endpoint_text":"- - Percentage of patients with BRCA wild-type HRP disease (%)","definition_or_measurement_approach":"Proportion of patients with BRCA wild-type HRP disease."}
• {"endpoint_text":"- - Tests/assays used (names, proprietary), and percentage of each of them (%)","definition_or_measurement_approach":"Documentation and proportion of different assays/tests used for biomarkers."}
• {"endpoint_text":"- - Incremental cost-utility ratio and incremental cost-effectiveness ratio","definition_or_measurement_approach":"Health economic endpoints calculated for cost-utility and cost-effectiveness analyses."}
• {"endpoint_text":"- - Net financial impact over 5 years","definition_or_measurement_approach":"Budget impact analysis calculating net financial impact over a 5-year horizon."}
• {"endpoint_text":"- - Percentage of patients operated with late complete debulking surgery, regardless of the number of chemotherapy cycles received","definition_or_measurement_approach":"Proportion of patients undergoing late complete debulking surgery irrespective of number of chemotherapy cycles."}

France

Earliest CTIS Part Ii Submission Date

11-04-2024

Latest Decision Or Authorization Date

26-11-2025

Processing Time Days

594

Number Of Sites

52

Number Of Participants

80

Italy

Earliest CTIS Part Ii Submission Date

25-10-2024

Latest Decision Or Authorization Date

27-11-2025

Processing Time Days

398

Number Of Sites

6

Number Of Participants

40

Netherlands

Earliest CTIS Part Ii Submission Date

18-08-2025

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

232

Number Of Sites

4

Number Of Participants

25

Primary sponsor

Full Name

Arcagy Gineco

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France