- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00030368
Bortezomib and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib when given in combination with paclitaxel in patients with locally advanced or metastatic solid tumors.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat every 3 weeks 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 of 3 or 2 of 6 patients experience dose-limiting toxicity or greater than 80% 20S proteasome inhibition. Once the MTD is determined, an additional 6-9 patients are accrued and treated at that dose.
Patients are followed at 21 days.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor for which there is no curative treatment
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal (ULN)
- Creatinine no greater than ULN
- Left ventricular function at least lower limit of normal if received prior doxorubicin
- No grade II or IV tilt-table test
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No thrombotic event within the past 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergic reaction to compounds of similar chemical or biological composition to study drugs
- No other concurrent uncontrolled illness
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Prior paclitaxel allowed
- At least 2 weeks since prior hormonal therapy
- No concurrent steroids or hormonal therapy except steroids to prevent hypersensitivity reactions to paclitaxel or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes)
- At least 4 weeks since prior radiotherapy
- At least 4 weeks since prior surgery
- Recovered from prior therapy
- No other concurrent investigational agents
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No concurrent anticoagulation therapy
- Concurrent pamidronate or zoledronate allowed for treatment of hypercalcemia or for palliation of skeletal metastases
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, paclitaxel)
Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8.
For the first course only, patients do not receive paclitaxel on day 1.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose-limiting toxicity (DLT) defined as Common Terminology Criteria (CTC) version 2.0 grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity with the exception of asymptomatic neutropenia [ANC < 500]
Time Frame: 21 days
|
21 days
|
Maximum-tolerated dose (MTD) based on the incidence of DLT
Time Frame: 21 days
|
21 days
|
Dose of PS-341 that results in not more than 70% to 80% 20S proteasome inhibition [20S-PI] in combination with a paclitaxel
Time Frame: At baseline and at 1 hour of weeks 1, 2 and 4
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At baseline and at 1 hour of weeks 1, 2 and 4
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response according to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Time Frame: Up to 21 days
|
Reported descriptively using all eligible patients and evaluable patients separately.
Response rates will include 95% confidence limits.
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Up to 21 days
|
Change in the level of p27 and Bax proteins in peripheral blood mononuclear cells
Time Frame: From baseline to 6 hours of day 1 (week 1) and day 2 (week 2)
|
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
|
From baseline to 6 hours of day 1 (week 1) and day 2 (week 2)
|
Change in plasma levels of TNF, IL-1, IL-6, and C-reactive protein
Time Frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
|
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
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From baseline to 6 hours of day 2 (weeks 1 and 2)
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Change in NF-kb biomarkers TRAP I and c-IAP-2 in tumor tissue blocks
Time Frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
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Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
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From baseline to 6 hours of day 2 (weeks 1 and 2)
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Change in phosphorylation of c-Jun and JNK in tumor tissue blocks
Time Frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
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Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
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From baseline to 6 hours of day 2 (weeks 1 and 2)
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Collaborators and Investigators
Sponsor
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-2012-01408
- U01CA076576 (U.S. NIH Grant/Contract)
- 0158
- NCI-1857
- CDR0000069159
- OSU-01H0147
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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