PS-341 and Doxorubicin in Treating Patients With Advanced Solid Tumors

University of Wisconsin (UW)

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: bortezomib; Drug: doxorubicin hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00023855

WCCC-CO-01901

P30CA014520 (U.S. NIH Grant/Contract)

CDR0000068870

NCI-3771

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of combining PS-341 and doxorubicin in treating patients who have advanced solid tumors.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of PS-341 in combination with doxorubicin in patients with advanced solid tumors.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of PS-341.

Patients receive PS-341 IV over 3-5 seconds on days 1, 4, 8, and 11; and doxorubicin IV on over 3-5 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-31 patients will be accrued for this study within 1 year.

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced solid tumor for which no curative treatment exists
• Measurable or evaluable disease
• No brain metastases or primary brain tumors

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• MUGA at least 45%

Other:

• No serious active infection
• No pre-existing neuropathy grade 2 or greater
• No other concurrent illness that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No prior cumulative dose of doxorubicin exceeding 280 mg/m^2

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational or commercial agents for treatment of this malignancy