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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028912
• Other study ID #: CDR0000069146
• Secondary ID: MSKCC-01097NCI-5
• Status: Completed
• Phase: Phase 1
• First received: January 4, 2002
• Last updated: April 23, 2011
• Start date: November 2001

Study information

• Verified date: April 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Drug:
• bortezomib

• carboplatin

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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.

Aghajanian C, Dizon DS, Sabbatini P, Raizer JJ, Dupont J, Spriggs DR. Phase I trial of bortezomib and carboplatin in recurrent ovarian or primary peritoneal cancer. J Clin Oncol. 2005 Sep 1;23(25):5943-9. — View Citation