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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Oliver Zivanovic, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01387399
First received: June 24, 2011
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Procedure: Cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Intraoperative Hyperthermic Intraperitoneal Chemoperfusion With Cisplatin in Patients With Recurrent Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • Dose-limiting toxicity [ Time Frame: within the first 21days after surgery ] [ Designated as safety issue: Yes ]
    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:
  • Pharmacokinetics [ Time Frame: within 24 hours of HIPEC ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Measure the effect of cisplatin as HIPEC on the ability to subsequently administer 6 cycles of standard intravenous platinum-based systemic chemotherapy.


Estimated Enrollment: 9
Study Start Date: June 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin as HIPEC
Phase I dose escalating study of cisplatin administered intraoperatively as hyperthermic intraperitoneal chemoperfusion
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01387399

Locations
Germany
University Hospital
Bonn, Germany, 53127
Sponsors and Collaborators
University Hospital, Bonn
Investigators
Principal Investigator: Oliver Zivanovic, MD University Hospital, Bonn
  More Information

No publications provided

Responsible Party: Oliver Zivanovic, Priv. Doz. Dr. med. Oliver Zivanovic, University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT01387399     History of Changes
Other Study ID Numbers: EudraCT No.: 2010-024652-28
Study First Received: June 24, 2011
Last Updated: February 14, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital, Bonn:
ovarian cancer
recurrence
platinum-sensitive recurrent ovarian cancer
HIPEC
intraperitoneal chemotherapy
hyperthermic intraperitoneal chemoperfusion
cisplatin
Platinum-sensitive recurrent ovarian cancer

Additional relevant MeSH terms:
Fever
Ovarian Neoplasms
Body Temperature Changes
Signs and Symptoms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014