Hyperthermic Intraoperative Intraperitoneal Chemotherapy of Recurrent Ovarian Cancer - A Feasibility Study
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Fitness for Systemic Chemotherapy
研究概览
简要总结
Most studies performing hyperthermic intraoperative intraperitoneal chemotherapy dose the cytotoxic drugs according to the body surface (like 50 mg/m² cisplatin) in analogy to systemic, intravenous chemotherapy (usually using the same dose). Although there seems to be a correlation between body surface and blood volume, the pharmacodynamics of drugs dosed by the body surface is still highly variable and thus dosing on the body surface is increasingly considered controversial for systemic administration.
For hyperthermic intraoperative intraperitoneal chemotherapy dosing by the body surface makes even less sense, since the aim is the highest possible drug concentration in the peritoneum without undue local and systemic toxicity. Furthermore, most studies using intraoperative chemotherapy vary the volume of the perfusate according to the size of the patient. Since the amount of cytotoxic drug is already fixed by the dosing on the body surface (amount [mg] = dose [mg/m²] x body surface [m²]) the effective concentration (mg/l) in the perfusate can vary considerably between patients. On the other hand pharmacokinetic analyses have shown that reducing the concentration of the cytotoxic drug in the perfusate reduces the efficacy even if the amount of the drug remains the same.
In this study the safety of a new dosing regime will be evaluated. The concentration of cisplatin in the perfusate will be held constant independent of body weight or size to achieve the highest effectiveness of the chemotherapy. The primary endpoint is the safety of the treatment. All patients should be able to receive full dose systemic carboplatin chemotherapy after completion the trial treatment.
详细描述
Disease Background:
Between 1997 and 2001 the incidence of ovarian cancer in Switzerland was 15.8 per 100'000 women and ranks fifth among the cancer incidence in women. Nearly half of the patients die of the disease leading to a mortality rate of 7.7 per 100'000. Together with pancreatic cancer, ovarian cancer ranks fifth among cancer related deaths in women. The most common form of ovarian cancer is the epithelial ovarian cancer with an incidence of 91.1%. Thus, in the following the term ovarian cancer will refer solely to malignant epithelial ovarian cancer (78.6% of all ovarian cancers) excluding borderline or low malignancy epithelial ovarian tumors (12.5%).
Early stages of the disease (FIGO I - IIA) show practically no symptoms, thus 80% of ovarian cancers are diagnosed at later stages (FIGO IIB - IV), a main reason for the high mortality. Treatment for all stages are surgical removal of visible and resectable tumor nodules, ovaries, uterus, omentum, pelvic and paraaortic lymph nodes, in advanced stages tumor infested organs or organ parts have to be removed (=cytoreduction or debulking). Survival time strongly depends on the completeness of the cytoreduction. Surgery is followed by a chemotherapy of carboplatin and paclitaxel or carboplatin alone (except for the low risk FIGO stage IA, G1).
Published survival rates after therapy vary considerably and are mainly dependent on the stage of the tumor and the remaining tumor size (some tumor masses cannot be resected due to the proximity to vital organs like major blood vessels).
_____Stage______survival after 5 years
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient with histologically confirmed and recurrent epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma requiring secondary debulking. Last chemotherapy of primary treatment was finished at least 6 months before.
- •Patient must give written informed consent before registration
- •WHO/ECOG performance status 0 - 1
- •Age ≥18 years, ≤70 years
- •Adequate hematological values: leukocytes ≥3x10^9/l, thrombocytes ≥100x10^9/l
- •Adequate renal function. Obstructive hydronephrosis as a cause of "borderline" (30 - 45 ml/min) renal function should be investigated and treated prior to study entry.
- •Patient compliance and geographic proximity allow proper staging and follow-up.
- •FIGO III and IV
排除标准
- •Primary diagnosis of epithelial ovarian cancer, or primary treatment completed less than 6 months ago.
- •FIGO stage I + II
- •Distant and current metastases
- •WHO/ECOG performance status ≥2
- •Inadequate hepatic function: bilirubin >1.5x ULN (upper limit normal range) or ASAT/ALAT >2.5x ULN or AP >5x ULN
- •Psychiatric disorder precluding understanding of information of trial related topics or giving informed consent
- •Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry
- •Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes)
- •Known hypersensitivity to cisplatin
- •Any concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic-approved product information
- •Dehydration
- •Impaired hearing or symptomatic peripheral neuropathy: ≥grade II NCI-CTCAEv3
- •Regular use of anti-epileptics
研究组 & 干预措施
HIPEC treatment
Cytoreduction
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with cisplatin
Perfusion of the peritoneum with 42°C warm 25 mg/l cisplatin solution. Perfusion volume depends on body size (3 - 6 l).
If cisplatin amount exceeds the equivalent of 62.5 mg/m² body surface, cisplatin is dosed by body surface (62.5 mg/m²)(safety margin).
Perfusion is performed with the open or Coliseum technique for 90 min.
干预措施: Hyperthermic intraoperative intraperitoneal chemotherapy (Procedure)
HIPEC treatment
Cytoreduction
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with cisplatin
Perfusion of the peritoneum with 42°C warm 25 mg/l cisplatin solution. Perfusion volume depends on body size (3 - 6 l).
If cisplatin amount exceeds the equivalent of 62.5 mg/m² body surface, cisplatin is dosed by body surface (62.5 mg/m²)(safety margin).
Perfusion is performed with the open or Coliseum technique for 90 min.
干预措施: Cytoreduction (Procedure)
HIPEC treatment
Cytoreduction
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with cisplatin
Perfusion of the peritoneum with 42°C warm 25 mg/l cisplatin solution. Perfusion volume depends on body size (3 - 6 l).
If cisplatin amount exceeds the equivalent of 62.5 mg/m² body surface, cisplatin is dosed by body surface (62.5 mg/m²)(safety margin).
Perfusion is performed with the open or Coliseum technique for 90 min.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Fitness for Systemic Chemotherapy
时间窗: 3 months post operation
Are patients fit to receive six courses of systemic carboplatin chemotherapy after completion of trial. If chemotherapy starts within 3 months after surgery and at least 4 courses could be administered, patient is considered fit. If chemotherapy is stopped early for reasons clearly unrelated to study treatment (e.g. platinum resistance), patient is also considered fit.
次要结局
- Overall Survival(5 years)
- Pharmacokinetics(intraoperative and 1 week after surgery)
- Nephrotoxicity(6 weeks post operation)
- Surgical Complications(6 weeks post operation)
研究者
Sascha Müller
Oberarzt
Cantonal Hospital of St. Gallen