Vorinostat and Flavopiridol in Treating Patients With Advanced Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: alvocidib (Drug); vorinostat (Drug); pharmacological study (Procedure)
Phase: Phase 1
Status: Recruiting
Sponsored by: Memorial Sloan-Kettering Cancer Center Official(s) and/or principal investigator(s):
Gary K. Schwartz, MD, Study Chair, Affiliation: Memorial Sloan-Kettering Cancer Center
Summary
RATIONALE: Drugs used in chemotherapy, such as vorinostat and flavopiridol, work in different
ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. Giving vorinostat together with flavopiridol may kill more tumor
cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when
given together with flavopiridol in treating patients with advanced solid tumors.
Clinical Details
Official title: A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors
Study design: Treatment, Non-Randomized, Open Label
Primary outcome: Maximum tolerated dose
Secondary outcome: Clinical pharmacokinetics of vorinostat (SAHA)Therapeutic activity of SAHA and flavopiridol Expression of p21, p53, and apoptotic markers relative to treatment response from baseline to 2 weeks after completion of study treatment
Detailed description:
OBJECTIVES:
- Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with
flavopiridol in patients with advanced solid tumors.
- Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these
patients.
- 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 flavopiridol 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 flavopiridol.
Once the MTD of SAHA in combination with fixed-dose flavopiridol 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 flavopiridol IV over 30 minutes followed by flavopiridol 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 flavopiridol.
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.
PROJECTED ACCRUAL: Approximately 60 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- 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
Locations and Contacts
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States; Recruiting
Gary K. Schwartz, MD, Phone: 212-639-8324
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 2006
Last updated: July 23, 2008
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