Bortezomib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00027898

Last Updated: 2013-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31

Brief Summary

Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of combining bortezomib with carboplatin and etoposide in treating patients who have advanced solid tumors that have not responded to previous treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.

II. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of bortezomib, etoposide, and carboplatin.

Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 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 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients with newly diagnosed, chemotherapy-naive extensive stage small cell lung cancer, and 6 patients with other tumor types, are treated at that dose.

PROJECTED ACCRUAL: A total of 12-27 patients will be accrued for this study within 6-14 months.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bortezomib, carboplatin, and etoposide)

Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

etoposide

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

bortezomib

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

etoposide

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

LDP 341; MLN341; VELCADE; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin; EPEG; VP-16; VP-16-213; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed advanced solid tumor cancer for which no curativetherapy exists
• Clinically stable CNS disease is allowed provided the following criteria are met:

• No uncontrolled brain metastases or CNS involvement
• No active seizures
• On stable dose of antiseizure or steroid medication for at least 7 days before study enrollment
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2.5 times upper limit of normal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No other serious concurrent systemic disorders (including other malignancy)
• No prior bone marrow or peripheral blood stem cell transplantation
• No concurrent immunotherapy
• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior carboplatin and/or etoposide allowed
• No more than 2 prior courses of mitomycin
• See Disease Characteristics
• No concurrent hormonal therapy
• At least 4 weeks since prior radiotherapy and recovered
• Palliative radiotherapy involving less than 35% bone marrow reserve allowed if completed at least 2 weeks before study enrollment
• No prior wide-field radiotherapy to 35% or more of bone marrow
• No prior pelvic radiotherapy
• No concurrent radiotherapy
• At least 28 days since prior investigational agents
• No other concurrent experimental medications

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lia Gore

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado

Denver, Colorado, United States

Countries

United States

Other Identifiers

COMIRB 01-288

Identifier Type: -

Identifier Source: secondary_id

U01CA099176

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069091

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02432

Identifier Type: -

Identifier Source: org_study_id