A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated doses of vorinostat (SAHA) and capecitabine
Safety Issue:
Yes
Principal Investigator
Eric X. Chen, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Princess Margaret Hospital, Canada
Authority:
United States: Federal Government
Study ID:
CDR0000434850
NCT ID:
NCT00121277
Start Date:
September 2005
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
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