CISPLATIN for Epithelial ovarian cancer | Fallopian tube cancer | Peritoneal carcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥18 years and ≤ 76 years"}
• {"criterion_text":"- Patient is 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"}
• {"criterion_text":"- Signed, IRB-approved written informed consent"}
• {"criterion_text":"- Patient covered by the French or Belgian “Social Security” regime"}
• {"criterion_text":"- Criteria to be checked per-operatively for confirmation of enrolment and randomization : Residual disease after surgery CC-0 (no macroscopic residue) or CC-1 (residue < 2.5 mm)"}
• {"criterion_text":"- Criteria to be checked per-operatively for confirmation of enrolment and randomization : Per-operative hemorrhage < 2.5 L"}
• {"criterion_text":"- Criteria to be checked per-operatively for confirmation of enrolment and randomization : Strictly less than 3 digestive resections (other than appendectomy) performed during surgery"}
• {"criterion_text":"- Criteria to be checked per-operatively for confirmation of enrolment and randomization : Diuresis maintained during surgery, without oliguria or anuria (per-operatory diuresis ≥ 0,5 mL/ kg/ h)"}
• {"criterion_text":"- Histologically proven primary epithelial ovarian carcinoma or fallopian tube carcinoma or peritoneal carcinoma (serous papillary adenocarcinoma, clear-cell carcinoma, mucinous adenocarcinoma and endometrioid carcinoma). In case of Primary Debulking Surgery (PDS), the patient can be included based on an extemporaneous diagnosis of stage III invasive carcinoma."}
• {"criterion_text":"- Pre-therapeutic FIGO stage III"}
• {"criterion_text":"- Patient eligible for a. Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy b. Or Interval Debulking Surgery (IDS) after neo-adjuvant chemotherapy +/- bevacizumab or other targeted therapy, with or without planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy. In case of neo-adjuvant chemotherapy, surgery should be performed in a time interval of 3 to 5 weeks in case of chemotherapy without bevacizumab, and in a time interval of 4 to 6 weeks if chemotherapy is combined with bevacizumab. The patient remains eligible for the trial if surgery is delayed beyond the recommended time interval."}
• {"criterion_text":"- WHO Performance Status ≤ 2"}
• {"criterion_text":"- Physical status score ASA2 ≤ 2 or ASA = 3 if only related to a BMI ≥ 40 or to malignant ascites"}
• {"criterion_text":"- Adequate bone marrow and renal function, as evidenced by the following tests performed within 7 days prior to surgery: - Absolute Neutrophil Count (ANC) ≥1,500/mm3 - Platelets ≥100,000/mm3 - Aspartate aminotransferase (ALT)/ Alanine aminotransferase (ALT) ≤2.5 × upper normal limit (UNL) (≤5.0 × ULN in case of liver metastases) - Total bilirubin ≤1.5 × ULN (except in case of Gilbert’s disease) - Creatinine clearance ≥ 60 mL/ min/ 1.73m2 (estimated according to MDRD formula)"}
• {"criterion_text":"- Negative serum pregnancy test within 7 days prior to surgery for women of childbearing potential. For non-menopaused women, if no hysterectomy is planned, willing to accept the use of an effective contraceptive regimen3 during the treatment period and at least 6 months after the end of treatment (surgery or adjuvant chemotherapy)"}
• {"criterion_text":"- Absence of contraindication to receive the products used in this study (cisplatin and products used in neo-adjuvant/ adjuvant chemotherapy) according to the most recent SmPC of these products (available at http://base-donnees-publique.medicaments.gouv.fr/)"}

Exclusion criteria

• {"criterion_text":"- Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma"}
• {"criterion_text":"- Pregnant or breastfeeding woman"}
• {"criterion_text":"- Psychiatric illness or social situation that would limit compliance with study requirement, substantially increase the risk of side effects, or compromise the ability of the patient to give written informed consent"}
• {"criterion_text":"- Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)"}
• {"criterion_text":"- Person under guardianship or curatorship"}
• {"criterion_text":"- Cirrhosis"}
• {"criterion_text":"- Known hypersensitivity to any of the trial drugs, trial drug classes, or excipients in the formulation"}
• {"criterion_text":"- Auditory impairment (i.e. if hearing aid is fitted or if the patient is complaining. In cases of doubt, an audiogram should be performed.)"}
• {"criterion_text":"- Dehydration or intercurrent disease that contraindicates hyperhydration (including cardio-respiratory disease)"}
• {"criterion_text":"- Other uncontrolled intercurrent disease including, but not limited to: diabetes; hypertension; symptomatic congestive heart or pulmonary failure; renal, hepatic or severe gastrointestinal (associated with diarrhea) chronic disease"}
• {"criterion_text":"- Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia), or NCI-CTCAE Grade ≥ 3 for anemia"}
• {"criterion_text":"- Concomitant treatment with prophylactic phenytoin"}
• {"criterion_text":"- Receipt of live attenuated vaccine, including yellow fever vaccine, within 30 days prior to inclusion (and, if patient is enrolled, up to 30 days after the last administration of study treatment)"}

Primary endpoints

• {"endpoint_text":"- Disease-Free Survival (DFS) will be computed as the time interval between randomization and progression, relapse or death from any cause. Progression and relapses will be assessed according to GCIG criteria1 and ideally confirmed by local tumor board. For patients alive without progression or relapse, data will be censored at the date of last follow-up visit.","definition_or_measurement_approach":"DFS is defined as time from randomization to progression, relapse or death from any cause; progression/relapse assessed according to GCIG criteria and ideally confirmed by local tumor board; censoring at date of last follow-up for patients alive without event."}

Secondary endpoints

• {"endpoint_text":"- Overall survival : OS will be computed as the time interval between randomization and death from any cause. For patients alive, data will be censored at the date of last follow-up.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; censor at last follow-up for survivors."}
• {"endpoint_text":"- Adverse events will be evaluated according to NCI-CTCAE V5.0 over the whole treatment duration from randomization up to the end of treatment (surgery or chemotherapy) plus 30 days, excluding AE unequivocally related to the disease under study or its progression. Adverse events of grade 3 or more (grade 3+) will be counted as severe adverse events.","definition_or_measurement_approach":"AEs graded per NCI-CTCAE v5.0 from randomization until end of treatment plus 30 days; grade ≥3 counted as severe; disease-related AEs excluded."}
• {"endpoint_text":"- The impact of HIPEC on the feasibility of adjuvant treatment will be assessed by describing the time interval between surgery and start of adjuvant chemotherapy. We will consider that start of chemotherapy is delayed if this time interval is larger than 6 weeks. In this case, the reasons will be described. - describing the total number of chemotherapy courses (neo-adjuvant+adjuvant). If the total number of chemotherapy course is below the planned number of 6, the reasons will be described.","definition_or_measurement_approach":"Feasibility measured by time from surgery to start of adjuvant chemotherapy; delay defined as >6 weeks; total number of chemotherapy courses counted (neo-adjuvant + adjuvant) and reasons documented if <6."}
• {"endpoint_text":"- Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) computed from survival times (overall survival and progression-free survival) and adverse events data (date of occurrence of grade 3+ adverse event) as detailed in the statistical considerations.","definition_or_measurement_approach":"Q-TWiST computed from OS and PFS and AE data (dates of grade ≥3 events) per statistical analysis plan."}
• {"endpoint_text":"- Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Score 30 (QLQ-C30), and Quality of Life Questionnaire–Ovarian Cancer Module (QLQ-OV28)","definition_or_measurement_approach":"Quality of life measured with EORTC QLQ-C30 and QLQ-OV28 instruments."}
• {"endpoint_text":"- Exploratory endpoint : Count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids","definition_or_measurement_approach":"Residual viable cell count assessed by flow cytometry on abdominal drainage fluids (for certain centres as specified)."}
• {"endpoint_text":"- Exploratory endpoint : Further research projects on the constituted biobank (tumor samples and blood samples) could be performed if additional and specific funding is obtained","definition_or_measurement_approach":"Biobank samples (tumor and blood) stored for potential future translational research subject to additional funding and approvals."}

Other endpoints

• {"endpoint_text":"- Exploratory endpoint : Count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids","definition_or_measurement_approach":"Flow cytometry count of residual viable cells in abdominal drainage fluids (site-specific: e.g., Centre Oscar Lambret only as noted in objectives)."}
• {"endpoint_text":"- Exploratory endpoint : Further research projects on the constituted biobank (tumor samples and blood samples) could be performed if additional and specific funding is obtained","definition_or_measurement_approach":"Constitution of a biobank (tumor and blood samples) for future translational research contingent on funding and approvals."}

France

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

01-10-2025

Processing Time Days

342

Number Of Sites

14

Number Of Participants

300

Belgium

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

02-10-2025

Processing Time Days

343

Number Of Sites

2

Number Of Participants

52

Primary sponsor

Full Name

Centre Oscar Lambret

Organisation Type

Pharmaceutical company

Country Of Registered Address

France