Phase III Randomized Clinical Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer Considering Two Different Settings: Primary Debulking Surgery (PDS) and Interval Debulking Surgery (IDS)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 362
- 试验地点
- 32
- 主要终点
- Disease-free Survival (DFS)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pre-eligibility criteria to be checked before surgery for pre-registration
- •Age ≥18 years and ≤ 76 years
- •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)
- •Pre-therapeutic FIGO (International Federation of Gynecology and Obstetrics) stage III
- •Patient eligible for
- •Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy
- •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.
- •WHO (World Health Organization Performance Status) ≤ 2
- •Physical status score ASA (American Society of Anesthesiologists) ≤ 2
- •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
- •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)
- •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
- •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
- •Signed written informed consent
- •Patient covered by the French or Belgian "Social Security" regime Criteria to be checked per-operatively for confirmation of enrolment and randomization
- •Residual disease after surgery (cytoreduction score CC) CC-0 (no macroscopic residue) or CC-1 (residue < 2.5 mm)
- •Per-operative hemorrhage < 2.5 L
- •Strictly less than 3 digestive resections performed during surgery
- •Diuresis maintained during surgery, without oliguria or anuria (per-operatory diuresis ≥ 0,5 mL/ kg/ h)
排除标准
- •Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma
- •Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
- •Auditory impairment
- •Dehydration or intercurrent disease that contraindicates hyperhydration (including cardio-respiratory disease)
- •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
- •Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia)
- •Concomitant treatment with prophylactic phenytoin
- •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)
- •Pregnant or breastfeeding woman
- •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
- •Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)
- •Person under guardianship
研究组 & 干预措施
Arm A (PDS or IDS + HIPEC)
Surgery (Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS)) + Neo or Adjuvant chemotherapy (standard care) + HIPEC (hyperthermic intraperitoneal chemotherapy)
Patients in this experimental arm will receive surgery (either PDS or IDS) and Neo and/or Adjuvant chemotherapy (CT) (as per standard care) combined with HIPEC. Patients undergoing PDS will also be receiving 6 cycles adjuvant CT according to the standard care (ideally 6 weeks post-surgery).
Patient undergoing IDS will start with 6 cycles of neo-adjuvant CT with a 3 - 5 weeks washout period (4 - 6 weeks if administered Bevacizumab) prior to surgery. They may also undergo additional adjuvant CT post-surgery according to the standard care.
干预措施: HIPEC (Drug)
Arm B (PDS or IDS)
Surgery (Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS)) + Neo or Adjuvant chemotherapy ONLY (standard care, without HIPEC)
Patients in the control group will ONLY receive the standard care, which consists of surgery (PDS or IDS) with Neo and/or Adjuvant chemotherapy (CT). Patients undergoing PDS will be receiving 6 cycles adjuvant CT according to the standard care (ideally 6 weeks post-surgery).
Patient undergoing IDS will start with 6 cycles of neo-adjuvant CT with a 3 - 5 weeks washout period (4 - 6 weeks if administered Bevacizumab) prior to surgery. They may also undergo additional adjuvant CT post-surgery according to the standard care.
结局指标
主要结局
Disease-free Survival (DFS)
时间窗: 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.
次要结局
- Overall survival(From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years..)
- Adverse events (AE)(Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days.)
- Quality of life of the patient (QLQOV28)(Up to 2 years after the end of treatment (every 3 month))
- Q-TWiST(Over the 5 year surveillance period)
- Quality of life of the patient (QLQC30)(Up to 2 years after the end of treatment (every 3 month))