Hyperthermic Intraoperative Intraperitoneal Chemotherapy of Recurrent Ovarian Cancer - A Feasibility Study

• Status: Terminated
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cantonal Hospital of St. Gallen
• Treatments: Cisplatin

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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