Bortezomib and Docetaxel in Treating Patients With Advanced Solid Tumors

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049088
First received: November 12, 2002
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: docetaxel
Biological: bevacizumab
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the NCI Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Toxicity and tolerability as assessed by NCI CTC version 2.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of docetaxel [ Time Frame: At baseline, at 30 and 60 during infusion, at 10 min, 30 min, 1, 3, 7.5, 24, and 48 hours, and at 8 days after completion of docetaxel infusion ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
  • 20S proteasome activity [ Time Frame: At 1 hour after first PS-341 infusion (week 2, day 2), and at 24 and 48 hours ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: August 2002
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00049088

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Sponsors and Collaborators
Investigators
Principal Investigator: Deborah Armstrong Johns Hopkins University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049088     History of Changes
Other Study ID Numbers: NCI-2012-02508, J0203, U01CA070095, CDR0000257807
Study First Received: November 12, 2002
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Antibodies
Antibodies, Monoclonal
Docetaxel
Bevacizumab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014