Intensive Intraperitoneal Therapy in Advanced Ovarian Cancer Combining Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Postoperative Intraperitoneal Chemotherapy (IPC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- The success of HIPEC and IPC combination assessed by surveillance safety
研究概览
简要总结
Clinicians postulate that it may be interesting to combine the two IntraPeritoneal (IP) treatments associated with a significant improvement of OC overall survival i.e. cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and postoperative intraperitoneal chemotherapy (IPC) as an " intensive peritoneal " regimen in the initial management of stages III-IVA ovarian cancers. Performing a postoperative IPC may allow completing and extending the duration of the effect of HIPEC in decreasing the risk of peritoneal recurrence. HIPEC may also allow administering an early IP treatment on the residual microscopic disease during initial or interval surgery with an optimal access to the intraperitoneal cavity. Postoperative IPC will extend the HIPEC effect on unsterilized peritoneal microscopic residues with the aim of decreasing the risk of local recurrence. Performing HIPEC before IPC could allow limiting the number of postoperative IP courses needed. Nevertheless, this association questions its feasibility and tolerance, which should both be assessed in a phase II trial. Clinicians propose to conduct this feasibility study combining for the first time HIPEC with IPC as first-line treatment of ovarian cancer with peritoneal carcinomatosis to perform a peritoneal intensification.
详细描述
Epithelial ovarian cancer (EOC) is the main cause of gynecological cancer death in developed countries, reflecting a clinical diagnosis possible at an advanced-stage of the disease and an early propensity for peritoneal dissemination. The treatment of these advanced stages combines optimal cytoreductive surgery and a platinum and taxan-based systemic chemotherapy. Despite a very high initial chemosensitivity and frequent clinical complete responses, the majority of patients relapses after a mean period of 18 months and progressively develops resistance to the various chemotherapeutic treatments. Nevertheless, recurrences remain frequently located in the peritoneal cavity.
Intraperitoneal administration of chemotherapeutic agents (intraperitoneal chemotherapy, IPC) is adapted to OC natural history. IPC has shown its clinical efficacy compared with intravenous (IV) chemotherapy in three randomized clinical trials. Recently, an unexpected median overall survival of 110 months was reported after complete surgery followed with IPC. Nevertheless, IPC repetitions are still strongly limited due to the high local toxicities and the difficult access to the peritoneal cavity leading to an important morbidity of the IP catheters. In the GOG-172 trial, half of the patients of the IPC arm did not receive the complete planned IP treatment. Long-term results of both the GOG-172 and GOG-114 trials showed that treatment efficacy is correlated with the numbers of IPC courses administered and with a significant long-term effect for patients receiving 3 or more IPC courses. For patients receiving neoadjuvant chemotherapy and optimal debulking surgery, the OV21 study recently showed that IP carboplatin-based chemotherapy was well tolerated and associated with an improved disease-free survival rate at 9 months after surgery compared with that of the IV chemotherapy group.
At the same time, complete cytoreductive surgery associated with perioperative hyperthermic intraperitoneal chemotherapy (i.e. HIPEC) is the second promising IP treatment that is currently evaluated in advanced OC. HIPEC allows an early IP treatment enhanced by hyperthermia while limiting the diffusion problem of the IP drugs and the difficult access to the peritoneal cavity. Nevertheless, despite this promising concept, HIPEC with a unique and limited IP cisplatin dose remains discussed in the management of OC. A phase 3 trial (OVHIPEC study), recently published in the New England Journal of Medicine, emphasized the therapeutic interest of a cisplatin-based HIPEC procedure at the time of interval surgery for patients receiving neoadjuvant chemotherapy. A significant improvement of overall survival (12 months gain: OS 33.9 months vs 45.7 months for IDS with HIPEC HR = 0.67 (0,48-0,94) p=0,02) was demonstrated for patients receiving HIPEC with a favorable tolerance profile and no additional morbidity.
Clinicians postulate that it may be interesting to combine the two IP treatments associated with a significant improvement of OC overall survival i.e. cytoreductive surgery with HIPEC and postoperative IPC as an " intensive peritoneal " regimen in the initial management of stages III-IVA ovarian cancers. Performing a postoperative IPC may allow completing and extending the duration of the effect of HIPEC in decreasing the risk of peritoneal recurrence. HIPEC may also allow administering an early IP treatment on the residual microscopic disease during initial or interval surgery with an optimal access to the intraperitoneal cavity. Postoperative IPC will extend the HIPEC effect on unsterilized peritoneal microscopic residues with the aim of decreasing the risk of local recurrence. Performing HIPEC before IPC could allow limiting the number of postoperative IP courses needed. Nevertheless, this association questions its feasibility and tolerance, which should both be assessed in a phase II trial. Clinicians propose to conduct this feasibility study combining for the first time HIPEC with IPC as first-line treatment of ovarian cancer with peritoneal carcinomatosis to perform a peritoneal intensification.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 to 75 years,
- •Patients with high-grade serous (high grade according to MD Anderson, grade II and III according to Silverman) ovarian or tubal or primitive peritoneal histologically proven cancer,
- •Initial laparoscopy confirming the histological type, evaluating the extent of the disease by PCI score and confirming the initial non-resectability,
- •Stage III B-C (FIGO 2014) or stage IVA with minimal or moderate pleural effusion (measured on a thoracic CT scanner, the largest thickness of which is less than 3 cm),
- •Complete interval cytoreduction surgery,
- •Indication of 3 to 4 cures of neoadjuvant chemotherapy based on the Carboplatin-Paclitaxel (carbo-taxol) combination,
- •The delay between the last course of NAT and the surgery must be between 4 and 8 weeks,
- •Hematologic function, hemoglobin ≥ 10 g / dl; PNN ≥ 1 x 109 / L, platelets ≥ 100 x 109 / L,
- •Total bilirubin ≤ 1.5 LSN, ALT or AST ≤ 3 ULN,
- •Absence of renal insufficiency (creatinine clearance ≤ 70 ml / min) according to the MDRD method,
- •Informed consent signed before any specific procedure under consideration,
- •Patients affiliated to the French social security scheme or equivalent.
排除标准
- •Performance Index (WHO) ≥ 2,
- •Stage IV B or IV A with significant pleural effusion (measured on a thoracic CT scanner, the largest thickness of which is more than 3 cm),
- •Renal impairment (clearance <70 ml / min) according to the MDRD method,
- •General contraindication to the realization of a tumor reduction surgery or HIPEC (contraindication or history allergic reaction to any treatments components),
- •Hepatic insufficiency (bilirubin > 1.5 x normal, ASAT & ALAT > 3 x upper limit of normal),
- •Serious life-threatening co-existing condition at stake,
- •Cardio-respiratory pathology indicating hyper hydration, to be implemented for HIPEC,
- •Patient who has already been treated with chemo-hyperthermia for ovarian cancer,
- •History of cancer, except basal cell carcinoma of the skin or carcinoma in situ of cervix having recurred within five years prior to entry into this trial,
- •Any severe untreated infectious disease,
- •Peripheral sensory neuropathy ≥ grade 2 at the inclusion time,
- •Patients whose regular follow-up is a priori impossible for psychological, family, social or geographical reasons,
- •Pregnant and / or nursing women,
- •Subjects under tutelage, curatorship or safeguard of justice.
研究组 & 干预措施
Intraperitoneal chemotherapy
Cisplatin 100mg/m2 during surgery IV Paclitaxel, 135mg/m2 on D1, IP Carboplatin, AUC 6 on D1, and IP Paclitaxel, 60mg/m2 on D8 after surgery with at least 3 courses performed (up to 4-6 allowed)
干预措施: Intraperitoneal chemotherapy during surgery (Drug)
结局指标
主要结局
The success of HIPEC and IPC combination assessed by surveillance safety
时间窗: Until the chemotherapy courses completion: 6 months after interval surgery
Rate of HIPEC tolerance (deterioration of the renal function and morbidity of HIVEC) and CIP tolerance (abdomibal pain and complications of the IP treatment)
The success of the combination of HIPEC and IPC assessed by chemotherapy administration after surgery
时间窗: Until the chemotherapy courses completion: 6 months after interval surgery
Number of administred courses of intraperitoneal chemotherapy during the 6 months following complete interval cytoreductive surgery with HIPEC.
次要结局
- Relapse-Free survival(Until study completion: 5 years)
- Morbidity rate of reductive surgery combined with HIPEC according to the CLAVIEN and DINDO score(Up to 60 postoperative days)
- IPC toxicities(Until the chemotherapy courses completion: 6 months after interval surgery)
- HIPEC toxicities(2 months after interval surgery)
- Complications(after interval surgery with HIPE: 2 months)