PS-341 and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00028587

Last Updated: 2013-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-12-31

Brief Summary

Phase I trial to study the effectiveness of combining PS-341 and combination chemotherapy in treating patients who have advanced solid tumors. PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining PS-341 and chemotherapy may kill more tumor cells

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib and paclitaxel administered in combination with carboplatin in patients with advanced solid tumors.

II. Compare the tolerability and efficacy of the different sequences of this regimen in these patients.

III. Determine the clinical toxic effects and pharmacokinetics of this regimen in these patients.

IV. Determine, preliminarily, the therapeutic activity of this regimen in these patients.

V. Evaluate p53 accumulation as a marker of PS-341 activity, and the effect of paclitaxel/carboplatin on PS-341 induced accumulation of p53.

VI. Exam the effect of PS-341 on the levels of other proteasome targets, e.g. mdm2, p27, p21, cyclins B, D1,E; IκB and other ubiquitinated proteins in tumor tissue, when available.

OUTLINE: This is a dose-escalation study of bortezomib and paclitaxel. Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.

Group B: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2.

Treatment in both groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. After 6 courses of paclitaxel and carboplatin, patients with stable or responding disease may continue with bortezomib alone at the discretion of the investigator. Cohorts of 3-6 patients in each group receive escalating doses of bortezomib and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 24-96 patients will be accrued for this study within 25 months.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group I (paclitaxel, carboplatin, bortezomib)

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Optional correlative studies

Group II (bortezomib, paclitaxel, carboplatin)

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Optional correlative studies

Interventions

bortezomib

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Optional correlative studies

Intervention Type: OTHER

Other Intervention Names

LDP 341; MLN341; VELCADE; Anzatax; Asotax; TAX; Taxol; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
• No hematologic malignancies
• No symptomatic CNS metastases

• Brain metastases allowed if previously treated (radiotherapy and/or surgery)and patient is stable for at least 8 weeks
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Creatinine no greater than 1.5 times ULN
• No New York Heart Association class III or IV heart disease
• HIV negative
• No peripheral neuropathy grade 2 or greater
• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy
• No prior bone marrow transplantation
• No concurrent immunotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 30% of bone marrow
• No concurrent radiotherapy
• No concurrent investigational ancillary therapy
• No concurrent enrollment in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Adjei

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

MC0012

Identifier Type: -

Identifier Source: secondary_id

CDR0000069108

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02436

Identifier Type: -

Identifier Source: org_study_id