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


Phase 1
N/A
N/A
Not Enrolling
Female
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Carol Aghajanian, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000069146

NCT ID:

NCT00028912

Start Date:

November 2001

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • recurrent ovarian epithelial cancer
  • primary peritoneal cavity cancer
  • fallopian tube cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms

Name

Location
Memorial Sloan-Kettering Cancer Center New York, New York  10021