A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

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

Name

Location