Adjusting chemotherapy for patients with poor prognosis ovarian cancer

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.