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

Ovarian Cancer Clinical Trial

— HIPEC ROC I  

Official title:

Phase I Study of Intraoperative Hyperthermic Intraperitoneal Chemoperfusion With Cisplatin in Patients With Recurrent Ovarian Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01387399
• Other study ID #: EudraCT No.: 2010-024652-28
• Status: Active, not recruiting
• Phase: Phase 1
• First received: June 24, 2011
• Last updated: February 14, 2013
• Start date: June 2011
• Est. completion date: July 2013

Study information

• Verified date: February 2013
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: July 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fever
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Procedure:
• Cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion
Classical "3+3" dose escalation study of cisplatin administered as HIPEC (60mg/m², 80mg/m² and 100mg/m²)

Locations

Country	Name	City	State
Germany	University Hospital	Bonn

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity	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).	within the first 21days after surgery	Yes
Secondary	Pharmacokinetics	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.	within 24 hours of HIPEC	Yes
Secondary	Number of cycles of standard intravenous platinum-based systemic chemotherapy	Measure the effect of cisplatin as HIPEC on the ability to subsequently administer 6 cycles of standard intravenous platinum-based systemic chemotherapy.	3 months	Yes