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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Hartford Hospital
Hartford, Connecticut, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Washington University School of Medicine
St Louis, Missouri, United States
Cooper Hospital University Medical Center
Camden, New Jersey, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
...and 4 more locations
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
Objective tumor response (complete and partial response)
Objective tumor response will be tabulated by regimen.
Time frame: Up to 1 year
Progression free survival
Will be summarized using Kaplan-Meier plots.
Time frame: Time from study entry to time of progression or death, whichever occurs first, assessed up to 1 year
Pharmacokinetic parameters
Descriptive analysis will be given for the pharmacokinetic parameters of bortezomib and carboplatin.
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
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