Bortezomib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors
A Phase I Study of PS-341 (NSC 681239), Carboplatin, and Etoposide in Patients With Advanced Solid Tumors Refractory to Standard Therapy
Study Overview
Status
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Colorado
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Denver, Colorado, United States, 80217-3364
- University of Colorado
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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.
|
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
MTD defined as the dose level below the dose level that results in DLT in >= 2 of 6 new patients assessed using NCI CTC version 2.0
Time Frame: 21 days
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21 days
|
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Biological data
Time Frame: Up to 4 years
|
The variation of these samples as a function of dose and time will be analyzed to define the mathematical function (e.g.
linear, exponential, logistic) that best fits and models the data.
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Up to 4 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lia Gore, University of Colorado, Denver
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2012-02432
- U01CA099176 (U.S. NIH Grant/Contract)
- COMIRB 01-288
- CDR0000069091 (Registry Identifier: PDQ (Physician Data Query))
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