Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00324480

Last Updated: 2014-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with alvocidib in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as vorinostat and alvocidib, 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 alvocidib may kill more tumor cells.

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

vorinostat

Intervention Type: DRUG

Given orally

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

alvocidib

Given IV

Intervention Type: DRUG

vorinostat

Given orally

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; pharmacological studies

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary Schwartz

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2009-00090

Identifier Type: REGISTRY

Identifier Source: secondary_id

MSKCC-05109

Identifier Type: -

Identifier Source: secondary_id

CDR0000472411

Identifier Type: -

Identifier Source: secondary_id

NCI-6858

Identifier Type: -

Identifier Source: secondary_id

05-109

Identifier Type: OTHER

Identifier Source: secondary_id

6858

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00090

Identifier Type: -

Identifier Source: org_study_id

NCT01645514

Identifier Type: -

Identifier Source: nct_alias

NCT01664377

Identifier Type: -

Identifier Source: nct_alias