- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00324480
Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors
A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.
II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.
III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib intravenously (IV) over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD of SAHA in combination with fixed-dose alvocidib. Once the MTD of SAHA in combination with fixed-dose alvocidib is determined, patients receive oral SAHA at one dose level below the MTD once daily on days 1-3 and 8-10 and divided-dose alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. If this schedule is well-tolerated, the MTD of SAHA in combination with divided-dose flavopiridol is determined as above. An additional 10 patients are treated at the MTD of SAHA in combination with divided-dose alvocidib. Patients undergo blood draws on days 1 and 9 of course 1 for pharmacokinetic analysis.
After completion of study treatment, patients are followed for 4 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically confirmed solid tumor
- Metastatic or unresectable disease
- Standard curative or palliative measures do not exist or are no longer effective
- No hematologic malignancies
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would preclude study compliance
- Recovered from prior therapy
- At least 2 weeks since prior histone acetylase inhibitors, including valproic acid
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- At least 2 weeks since prior investigational therapy
- At least 2 weeks since prior radiotherapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent commonly used vitamins, antioxidants, or herbal preparations and supplements
- A single tablet multivitamin is allowed
- No other concurrent anticancer agents or therapies for this mailgnancy
- No other concurrent investigational agents
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 (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug.
Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Correlative studies
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
Time Frame: Course 1
|
Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course.
Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
|
Course 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical pharmacokinetics of vorinostat (SAHA)
Time Frame: Week 1 of course 1
|
Week 1 of course 1
|
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Therapeutic activity of SAHA and flavopiridol
Time Frame: Not Provided
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Not Provided
|
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Expression of p21, p53, and apoptotic markers relative to treatment response
Time Frame: Baseline to 2 weeks after completion of study treatment
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Evaluated using immunohistochemistry.
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Baseline to 2 weeks after completion of study treatment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gary Schwartz, Memorial Sloan Kettering Cancer Center
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-2009-00090 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA069856 (U.S. NIH Grant/Contract)
- P30CA008748 (U.S. NIH Grant/Contract)
- 6858 (Other Identifier: CTEP)
- 05-109 (Other Identifier: Memorial Sloan-Kettering Cancer Center)
- MSKCC-05109
- CDR0000472411
- NCI-6858
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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