Vorinostat and Flavopiridol in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00324480

Purpose

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.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: alvocidib Drug: vorinostat Other: pharmacological study	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Alvocidib Flavopiridol Suberoylanilide hydroxamic acid

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Clinical pharmacokinetics of vorinostat (SAHA) [ Designated as safety issue: No ]
Therapeutic activity of SAHA and flavopiridol [ Designated as safety issue: No ]
Expression of p21, p53, and apoptotic markers relative to treatment response from baseline to 2 weeks after completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	March 2006
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324480

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Gary K. Schwartz, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000472411, MSKCC-05109, NCI-6858
Study First Received:	May 10, 2006
Last Updated:	May 5, 2009
ClinicalTrials.gov Identifier:	NCT00324480 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Vorinostat
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Protein Kinase Inhibitors
Pharmacologic Actions

Flavopiridol
Neoplasms
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Growth Inhibitors
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 27, 2009