Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	Not specified	NCI	MSKCC-01097 NCI-5326, NCT00028912, 5326

Objectives

1. 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.
2. Determine the toxicity of this regimen in these patients.
3. Determine the pharmacodynamics of this regimen in these patients by measurement of 20S proteasome inhibition in whole blood.
4. Correlate toxicity with 20S proteasome inhibition in a whole blood assay in patients treated with this regimen.

Entry 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

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

Patient Characteristics:

Age:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Aghajanian C, Dizon DS, Sabbatini P, et al.: Phase I trial of bortezomib and carboplatin in recurrent ovarian or primary peritoneal cancer. J Clin Oncol 23 (25): 5943-9, 2005.[PUBMED Abstract]

Aghajanian C, Dizon D, Yan XJ, et al.: Phase I trial of PS-341 and carboplatin in recurrent ovarian cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1815, 2003.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Carol Aghajanian, MD, Protocol chair		Ph: 212-639-2252; 800-525-2225 Email: aghajanC@mskcc.org

Registry Information
Official Title		Phase I Trial of Bortezomib (NSC 681239, IND#58443) and Carboplatin in Recurrent or Progressive Epithelial Ovarian Cancer or Primary Peritoneal Cancer
Trial Start Date		2001-11-14
Registered in ClinicalTrials.gov		NCT00028912
Date Submitted to PDQ		2001-11-13
Information Last Verified		2004-04-15
NCI Grant/Contract Number		P30-CA08748, U01-CA69856

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