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

Sponsor:	Princess Margaret Hospital, Canada
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00121277

Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat and capecitabine, 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 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 capecitabine in treating patients with unresectable or metastatic solid tumors.

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

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Suberoylanilide hydroxamic acid Capecitabine

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated doses of vorinostat (SAHA) and capecitabine [ Designated as safety issue: Yes ]
Safety and tolerability as assessed by CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
Molecular markers as assessed by molecular analysis [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	September 2005

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose and recommended phase II dose of vorinostat (SAHA) and capecitabine in patients with metastatic or unresectable solid tumors.
Determine the safety and tolerability of this regimen in these patients.

Secondary

Correlate the clinical effects with the pharmacokinetic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral vorinostat (SAHA) once or twice daily and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of CR. Patients achieving a partial response receive 2 courses beyond documentation of best response.

Cohorts of 3-6 patients receive escalating doses of SAHA and capecitabine 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. An additional 12 patients are treated at the MTD.

After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study within 6-10 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed malignant solid tumor
- Metastatic or unresectable disease
Standard curative or palliative measures do not exist or are no longer effective
Patients who received prior radiotherapy must have measurable disease outside a previously irradiated field OR disease progression after prior radiotherapy
No known brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

More than 12 weeks

Hematopoietic

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

Hepatic

Bilirubin normal
AST and ALT ≤ 2.5 times upper limit normal (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
Able to swallow oral medication
No clinical or radiological diagnosis of bowel obstruction
No ongoing or active infection
No history of allergic reaction attributed to compounds of similar chemical or biological composition to suberoylanilide hydroxamic acid or other agents used in this study
No known dihydropyrimidine dehydrogenase deficiency
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Prior fluorouracil allowed
No prior capecitabine

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy and recovered
No prior radiotherapy to > 40% of bone marrow

Surgery

At least 4 weeks since prior surgery and recovered

Other

At least 2 weeks since prior valproic acid
No other concurrent investigational agents
No other concurrent anticancer therapy
No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121277

Locations

Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Princess Margaret Hospital, Canada

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Eric X. Chen, MD, PhD

Princess Margaret Hospital, Canada

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:	CDR0000434850, PMH-PHL-035, NCI-6868
Study First Received:	July 19, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00121277 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Antimetabolites
Capecitabine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Vorinostat
Enzyme Inhibitors
Protective Agents

Pharmacologic Actions
Neoplasms
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010