Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	PMH-PHL-035 NCI-6868, 6868, NCT00121277

Objectives

Primary

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

Secondary

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

Entry 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

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

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/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

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

Outcomes

Maximum tolerated doses of vorinostat (SAHA) and capecitabine
Safety and tolerability as assessed by CTCAE v3.0

Response rate as assessed by RECIST criteria
Molecular markers as assessed by molecular analysis
Survival

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.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Eric Chen, MD, PhD, Principal investigator		Ph: 416-946-2263

Registry Information
Official Title		A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination with Capecitabine in Patients with Solid Tumors
Trial Start Date		2005-09-07
Registered in ClinicalTrials.gov		NCT00121277
Date Submitted to PDQ		2005-05-25
Information Last Verified		2007-10-15
NCI Grant/Contract Number		CM17107

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