Safety and Pharmacokinetics of Intraoperative Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) With Cisplatin to Treat Platinum-sensitive Recurrent Ovarian Cancer

Phase 1

• Conditions: Ovarian Cancer
• Interventions: Procedure: Cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion

• Registration Number: NCT01387399
• Lead Sponsor: University Hospital, Bonn

Brief Summary

The purpose of this phase I study is to determine the safety, feasibility, maximum tolerated dose (MTD), pharmacokinetics and pharmacodynamics of Cisplatin administered as Intraoperative Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) in Patients with Platinum-Sensitive Recurrent Ovarian Cancer.

Detailed Description

This is a phase I dose escalating study designed to identify tolerable, clinically active doses of cisplatin delivered as intraoperative intraperitoneal hyperthermic chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent ovarian cancer. After surgical cytoreduction, a single dose of cisplatin will be administered in 3 liters normal saline via intraperitoneal HIPEC with closed-abdomen technique for 90 minutes in the hyperthermic phase (41-43 degrees C). After completion of perfusion, the perfusate will be drained, the abdomen opened and the abdomen and pelvis irrigated with 2-3 liters normal saline to wash away any residual chemotherapeutic agent. Fascia and skin will then be closed in a standard fashion. Cisplatin infusion will be discontinued for unacceptable toxicity. The primary objective is to determine the maximum tolerated dose (MTD) of cisplatin administered as HIPEC. Secondary objectives are to determine pharmacokinetics and pharmacodynamics as well as the effect of cisplatin as HIPEC on the ability to subsequently administer 6 cycles of standard platinum-based systemic chemotherapy.

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-06-24
• Study First Submitted QC: 2011-07-01
• Study First Posted: 2011-07-04
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-14
• Last Update Posted: 2013-02-18
• Primary Completion: 2013-03
• Study Completion: 2013-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 9

Inclusion Criteria

• only female participants are being studied
• signed informed consent
• patients with histologically proven or suspicious recurrent epithelial ovarian cancer (based on Response Evaluation Criteria in Solid Tumors (RECIST)- or CA-125 criteria)
• Progression-free interval after completion of adjuvant platinum-based chemotherapy of 6 months or more.
• Subjects with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, adenocarcinoma N.O.S.
• Patients are eligible if the disease is deemed operable to equal or less than 1 cm at the completion of surgery.

Exclusion Criteria

• mucinous Ovarian cancer
• non-invasive Borderline tumor
• subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin are permitted, provided that it was completed more than 3 years prior to enrollment, and the subject remains free of recurrent or metastatic disease
• subjects with active infection that requires parenteral antibiotics
• patients with any underlying cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions, chronic or latent infectious diseases, immune deficiency, or history, which in the opinion of the investigator, places the patient at an unacceptable risk for participation in the study
• patients with known platinum allergy
• evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operating surgeon

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cisplatin as HIPEC	Cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion	Phase I dose escalating study of cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity	within the first 21days after surgery	To determine the safety and maximum tolerated dose (MTD) of cisplatin (60 mg/m², 80mg/m² and 100 mg/m²) administered as intraperitoneal hyperthermic chemoperfusion defined by the dose-limiting toxicity (DLT).

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics	within 24 hours of HIPEC	Blood and peritoneal concentrations of cisplatin will be measured at various time points within the first 24 hours after HIPEC. The elimination half-life and the area under the plasma concentration time curve of cisplatin will be measured. Peritoneal and systemic clearance and distribution of cisplatin will be modeled in a compartmental model.
Number of cycles of standard intravenous platinum-based systemic chemotherapy	3 months	Measure the effect of cisplatin as HIPEC on the ability to subsequently administer 6 cycles of standard intravenous platinum-based systemic chemotherapy.

Trial Locations

Locations (1)

University Hospital; 🇩🇪 Bonn, Germany