Vorinostat and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00243100

Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat and gemcitabine, 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 and by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and gemcitabine in treating patients with metastatic or unresectable solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: gemcitabine hydrochloride Drug: vorinostat	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Gemcitabine in Patients With Epithelial Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Suberoylanilide hydroxamic acid

U.S. FDA Resources

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

Primary Outcome Measures:

Dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously [ Designated as safety issue: Yes ]
Pharmacokinetics at first course [ Designated as safety issue: No ]

Secondary Outcome Measures:

Antitumor activity as measured by NCI RECIST criteria every 9 weeks [ Designated as safety issue: No ]
Gene expression profiling at pretreatment [ Designated as safety issue: No ]

Estimated Enrollment:	21
Study Start Date:	November 2005
Estimated Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the dose-limiting toxicity, maximum tolerated dose, and pharmacokinetics of vorinostat (SAHA) and gemcitabine in patients with metastatic or unresectable epithelial solid tumors.

Secondary

Determine tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation, open-label study.

Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine 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. A minimum of 6 patients are treated at the MTD.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 6-21 patients will be accrued for this study within 3-11 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed epithelial solid tumors
- Metastatic or unresectable disease
- No known standard curative or palliative therapies exist or are no longer effective
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion with minimum lesion size ≥ 2 times the slice thickness of the imaging study used
No brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness
No history of allergy, significant side effects, or poor tolerance to gemcitabine
No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA)

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

Not specified

Radiotherapy

At least 2 weeks since prior radiotherapy

Surgery

Not specified

Other

Recovered from prior therapy
More than 2 weeks since prior valproic acid
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational drugs
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00243100

Locations

United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Gauri Varadhachary, MD	M.D. Anderson Cancer Center
Investigator:	Renato Lenzi, MD	M.D. Anderson 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:	CDR0000445401, MDA-2005-0140, NCI-6865
Study First Received:	October 20, 2005
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00243100 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Anticarcinogenic Agents
Antimetabolites
Anti-Inflammatory Agents
Anti-Infective Agents
Immunologic Factors
Vorinostat
Antiviral Agents
Immunosuppressive Agents

Radiation-Sensitizing Agents
Analgesics, Non-Narcotic
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Gemcitabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Anticarcinogenic Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics

Gemcitabine
Vorinostat
Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Protective Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Analgesics, Non-Narcotic
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 10, 2009