Bortezomib and Docetaxel in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00049088

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31

Brief Summary

Phase I trial to study the effectiveness of combining bortezomib with docetaxel in treating patients who have advanced solid tumors. Bortezomib 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 bortezomib with docetaxel may kill more tumor cells

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib and docetaxel in patients with advanced solid tumors.

II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the biologic correlates of proteasome inhibition of bortezomib and determine the effects of this inhibition on the pharmacokinetics of docetaxel in these patients.

IV. Determine the antitumor efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest. For course 2 and all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2, 5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 2-6 patients receive escalating doses of bortezomib and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: A minimum of 24 patients will be accrued for this study.

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 (docetaxel, bevacizumab)

For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest. For course 2 and all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2, 5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 2-6 patients receive escalating doses of bortezomib and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

Given IV

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

docetaxel

Given IV

Intervention Type: DRUG

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

RP 56976; Taxotere; TXT; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed solid tumor for which standard curative or palliative measures do not exist or are no longer effective

• Metastatic or unresectable disease
• No known brain metastases
• Performance status - ECOG 0-2
• Performance status - Karnofsky 50-100%
• More than 12 weeks
• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL
• Bilirubin normal
• AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 5 times ULN (unless bone-derived) and AST and ALT less than 1.5 times ULN
• Creatinine normal
• Creatinine clearance at least 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study
• No prior allergic reactions attributed to taxanes (e.g., docetaxel or paclitaxel) or compounds of similar chemical or biological composition
• No prior allergic reactions to compounds similar to bortezomib or other study agents
• No known hypersensitivity to corticosteroids
• No predicted intolerance to regular, repeated administration of corticosteroids (e.g., poorly controlled diabetes or significant osteoporosis/osteopenia)
• No ongoing or active infection
• No other uncontrolled concurrent illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study participation
• No peripheral neuropathy grade 2 or greater
• At least 4 weeks since prior chemotherapy (6 weeks for carmustine, nitrosoureas, or mitomycin) and recovered

• No more than 3 courses of mitomycin
• Prior taxanes allowed

• At least 6 months since prior docetaxel administered on a weekly schedule
• At least 4 weeks since prior radiotherapy and recovered
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies (commercial or investigational)

• 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

Deborah Armstrong

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

J0203

Identifier Type: -

Identifier Source: secondary_id

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000257807

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02508

Identifier Type: -

Identifier Source: org_study_id