Bortezomib and Carboplatin in Treating Patients With Recurrent or Progressive Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Brief Title

Bortezomib and Carboplatin in Treating Patients With Recurrent or Progressive Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Official Title

Phase I Trial of Bortezomib (NSC 681239, IND#58443) and Carboplatin in Recurrent or Progressive Epithelial Ovarian Cancer or Primary Peritoneal Cancer

Brief Summary

      RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary
      for tumor cell growth. Drugs used in chemotherapy such as carboplatin use different ways to
      stop tumor cells from dividing so they stop growing or die. Bortezomib may help carboplatin
      kill more tumor cells by making tumor cells more sensitive to the drug.

      PURPOSE: Phase I trial to study the effectiveness of combining bortezomib with carboplatin in
      treating patients who have recurrent or progressive ovarian epithelial, primary peritoneal,
      or fallopian tube cancer.

Detailed Description

OBJECTIVES:

- Determine the maximum tolerated dose of bortezomib in combination with carboplatin in
patients with recurrent or progressive ovarian epithelial, primary peritoneal, or
fallopian tube cancer.

- Determine the toxicity of this regimen in these patients.

- Determine the pharmacodynamics of this regimen in these patients by measurement of 20S
proteasome inhibition in whole blood.

- Correlate toxicity with 20S proteasome inhibition in a whole blood assay in patients
treated with this regimen.

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

Patients receive carboplatin IV over 30 minutes on days 1 and 8 followed by 1 week of rest
during the first course of treatment. Beginning with the second course, patients receive
bortezomib IV on days 1, 4, 8, and 11 and carboplatin IV over 30 minutes on days 1 and 8.
Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 8 additional
patients are accrued and treated at that dose.

PROJECTED ACCRUAL: A total of 3-32 patients will be accrued for this study.

Study Phase

Phase 1

Study Type

Interventional

Condition

Fallopian Tube Cancer

Intervention

bortezomib

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Start Date

November 2001

Eligibility Criteria

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube
             cancer

               -  Recurrent or progressive disease

          -  Received at least 1 prior platinum-based chemotherapy regimen containing carboplatin,
             cisplatin, or another organoplatinum compound for primary disease

               -  May include high-dose therapy, consolidation, or extended therapy after surgical
                  or non-surgical assessment

          -  No brain metastases or leptomeningeal involvement

        PATIENT CHARACTERISTICS:

        Age:

          -  Not specified

        Performance status:

          -  Karnofsky 70-100%

        Life expectancy:

          -  Not specified

        Hematopoietic:

          -  Absolute neutrophil count at least 1,000/mm^3

          -  Platelet count at least 100,000/mm^3

          -  Hemoglobin at least 8.0 g/dL

        Hepatic:

          -  AST and ALT no greater than 2.5 times upper limit of normal

          -  Bilirubin no greater than 1.8 mg/dL

        Renal:

          -  Creatinine no greater than 1.5 mg/dL

        Cardiovascular:

          -  LVEF greater than 50% by radionuclide ventriculogram or two-dimensional echocardiogram

          -  No peripheral vascular disease requiring surgical management

          -  No prior myocardial infarction

          -  No congestive heart failure

          -  No orthostatic hypotension

          -  No acute ischemia or significant conduction abnormality (bifascicular block, defined
             as left anterior hemiblock with right bundle branch block, second or third degree AV
             blocks) as evidenced by electrocardiogram

          -  No prior cerebrovascular event

        Other:

          -  No peripheral neuropathy grade 2 or greater

          -  No other serious medical or psychiatric illness

          -  Not pregnant

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

        Biologic therapy:

          -  Not specified

        Chemotherapy:

          -  See Disease Characteristics

          -  No more than 2 prior regimens for recurrent disease, including 1 non-platinum
             containing regimen

          -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and
             recovered

        Endocrine therapy:

          -  At least 1 week since prior hormonal therapy directed at primary tumor

          -  Concurrent hormone replacement therapy allowed

        Radiotherapy:

          -  Not specified

        Surgery:

          -  See Disease Characteristics

          -  At least 2 weeks since prior major surgery

Gender

Female

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Carol Aghajanian, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT00028912

Organization ID

CDR0000069146

Secondary IDs

MSKCC-01097

Study Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Carol Aghajanian, MD, Study Chair, Memorial Sloan Kettering Cancer Center

Verification Date

April 2004