Clinical Trial: Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I Pharmacokinetic Study of Intraperitoneal CTEP-Supplied Agent Bortezomib (PS-341, NSC 681239) and Carboplatin (NSC# 241240) in Patients With Persistent or Recurrent Ovarian, Fallopian Tube, o

Brief Summary: This phase I trial studies the side effects and best dose of intraperitoneal bortezomib when given together with intraperitoneal carboplatin in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that is persistent or has come back. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may help carboplatin work better by making tumor cells more sensitive to the drug. Infusing bortezomib and carboplatin directly into the abdomen (intraperitoneal) may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intraperitoneal (IP) bortezomib (BTZ) when administered with intraperitoneal carboplatin in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer that is persistent or recurrent and who have failed primary therapy and at least one second-line therapy.

II. To examine the safety of administering BTZ in combination with carboplatin by the IP route.

SECONDARY OBJECTIVES:

I. To estimate objective tumor response rate as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

II. To determine the pharmacokinetic profile of BTZ and carboplatin when administered intraperitoneally once every 21 days.

III. To characterize the frequency of carboplatin hypersensitivity reactions (HSR) when administered as an intraperitoneal infusion in the context of recurrent ovarian cancer.

OUTLINE: This is a dose-escalation study of bortezomib.

Patients receive bortezomib intraperitoneally (IP) and carboplatin IP on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Dose-limiting toxicities defined by drug-related adverse events which occur in association with the first course of treatment as evaluated by the NCI CTCAE version 4 unless clearly unrelated to study drugs (e.g., disease progression) [ Time Frame: 21 days ]
  • Frequency and severity of toxicities as assessed by NCI CTCAE version 4 [ Time Frame: Up to 1 year ]


Original Primary Outcome:

  • Maximum-tolerated dose (MTD) of intraperitoneal (IP) bortezomib when administered with IP carboplatin
  • MTD of IP bortezomib when administered with IP carboplatin and pegfilgrastim
  • Dose-limiting toxicities during the first course of therapy
  • Frequency and severity of toxicities as assessed by NCI CTCAE criteria


Current Secondary Outcome:

  • Objective tumor response (complete and partial response) [ Time Frame: Up to 1 year ]
    Objective tumor response will be tabulated by regimen.
  • Pharmacokinetic parameters [ Time Frame: 10 minutes prior to infusion; immediately following infusion; 15, 30 and 60 minutes after infusion; immediately following carboplatin; 90 minutes after infusion; and 2, 4, and 6 hours after infusion ]
    Descriptive analysis will be given for the pharmacokinetic parameters of bortezomib and carboplatin.
  • Progression free survival [ Time Frame: Time from study entry to time of progression or death, whichever occurs first, assessed up to 1 year ]
    Will be summarized using Kaplan-Meier plots.


Original Secondary Outcome:

  • Objective tumor response (complete and partial response)
  • Pharmacokinetics of bortezomib


Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 23, 2010
Date Started: April 2010
Date Completion:
Last Updated: May 23, 2017
Last Verified: November 2016