Ovarian Cancer, Ovarian Carcinoma, Ovary Neoplasms
Conditions
Keywords
Ovarian cancer, Hyperthermic intraperitoneal chemotherapy, HIPEC, Primary Debulking Surgery, Interval Debulking Surgery
Brief summary
This is a phase III, multicenter, interventional and randomized study which evaluates the use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) coupled with either Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS), in patients with ovarian cancer. This study aims to assess the efficacy, in terms of disease-free survival (DFS), the use of HIPEC combined with standard care (PDS or IDS) or standard care alone.
Detailed description
The primary objective of this study is to assess the efficacy, in terms of disease-free survival (DFS), the use of HIPEC treatment combined with standard care (PDS or IDS) or standard care alone (PDS or IDS alone). Secondary objectives of the study include: * Evaluating the efficacy of HIPEC in terms of overall survival (OS) in combination with standard of care * Evaluating the morbidity associated with HIPEC. * Evaluating the trade-off between efficacy and morbidity using the Q-TWiST approach. * Evaluating the impact of HIPEC in terms of quality of life. Exploratory objectives (optional) include: * Evaluating the impact of HIPEC on the count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids for patients recruited in Centre Oscar Lambret only. * Constituting a biobank (tumoral samples and blood samples) for future translational researches
Interventions
DRUGHIPEC
HIPEC protocol (ONLY Arm A) consisted in cisplatin 100mg/m2 intraperitoneally (IP), heated to 40°C for 90 minutes, along with an IV perfusion of sodium thiosulfate. Administration of the dose should be according the following schedule: * 50% of the dose at start of perfusion, 25% of the dose after 30 minutes from start of the perfusion and 25% of the dose after 60 minutes from start of the perfusion. * The procedure takes 120 minutes with a 90-minute perfusion period. The IV perfusion of sodium thiosulfate is for renal protection. At the start of HIPEC procedure, 9 g/m2 in 200 ml of distilled water will be administered by IV over 15 to 30 minutes. It will be then followed by 12 g/m2 in 1 liter (1L) distilled water in a continuous IV for 6 hours.
Sponsors
Centre Oscar Lambret
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
Pre-eligibility criteria to be checked before surgery for pre-registration 1. Age ≥18 years and ≤ 76 years 2. Histologically proven primary epithelial ovarian carcinoma or fallopian tube carcinoma or peritoneal carcinoma (including serous papillary adenocarcinoma, clear-cell carcinoma, mucinous adenocarcinoma and endometrioid carcinoma) 3. Pre-therapeutic FIGO (International Federation of Gynecology and Obstetrics) stage III 4. Patient eligible for 1. Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy 2. 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 study if surgery is delayed beyond the recommended time interval. 5. WHO (World Health Organization Performance Status) ≤ 2 6. Physical status score ASA (American Society of Anesthesiologists) ≤ 2 7. 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 limit of normal (ULN) (≤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 8. Negative serum pregnancy test within 7 days prior to surgery for women of childbearing potential. For non-menopausal women, if no hysterectomy is planned, willing to accept the use of an effective contraceptive regimen during the treatment period and at least 6 months after the end of treatment (surgery or adjuvant chemotherapy) 9. 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 (Summary of Product Characteristics) of these products 10. 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 11. Signed written informed consent 12. Patient covered by the French or Belgian "Social Security" regime Criteria to be checked per-operatively for confirmation of enrolment and randomization 13. Residual disease after surgery (cytoreduction score CC) CC-0 (no macroscopic residue) or CC-1 (residue \< 2.5 mm) 14. Per-operative hemorrhage \< 2.5 L 15. Strictly less than 3 digestive resections performed during surgery 16. Diuresis maintained during surgery, without oliguria or anuria (per-operatory diuresis ≥ 0,5 mL/ kg/ h)
Exclusion criteria
1. Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma 2. Cirrhosis 3. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 4. Auditory impairment 5. Dehydration or intercurrent disease that contraindicates hyperhydration (including cardio-respiratory disease) 6. 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 7. Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia) 8. Concomitant treatment with prophylactic phenytoin 9. 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) 10. Pregnant or breastfeeding woman 11. 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 12. Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons) 13. Person under guardianship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | From randomization to first progression, relapse or death from any cause, whichever came first, assessed up to 5 years. (Follow-up up to 5 years) | The DFS will be measured to assess the efficacy of the combination treatment of surgery and HIPEC or standard care alone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years.. | The overall survival will be measured to assess the efficacy of HIPEC in combination with standard care. |
| Adverse events (AE) | Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days. | The adverse events (AE) are collected to evaluate the impact of HIPEC on the safety and on the feasibility of adjuvant treatment (if any) is planned after surgery. |
| Q-TWiST | Over the 5 year surveillance period | Q-Twist (Quality-adjusted time without symptoms of disease or toxicity) will be calculated from the survival tile (OS and DFS) and AE (adverse events) data. |
| Quality of life of the patient (QLQC30) | Up to 2 years after the end of treatment (every 3 month) | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Score 30 (QLQ-C30) will be used to measure the quality of life of the patients. |
| Quality of life of the patient (QLQOV28) | Up to 2 years after the end of treatment (every 3 month) | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Ovarian Cancer Module (QLQ-OV28) will be used to measure the quality of life of the patients. |
Countries
Belgium, France
Contacts
STUDY_DIRECTORFabrice NARDUCCI, MD
Centre Oscar Lambret, Lille, France
Outcome results
None listed