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A Phase 1 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Gemcitabine in Patients With Epithelial Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase 1 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Gemcitabine in Patients With Epithelial Tumors


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


II. 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.

Inclusion Criteria:

- ECOG 0-2 OR Karnofsky 60-100%

- AST and ALT =< 2.5 times ULN

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- Platelet count >= 100,000/mm3

- Absolute neutrophil count >= 1,500/mm3

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Any number and type of prior chemotherapies are allowed including prior use of
gemcitabine chemotherapy. A washout phase of at least 2 weeks since use of prior
chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas
or mitomycin C, is required.

- Patients must have histologically confirmed epithelial malignancy that is metastatic
or unresectable and for which standard curative or palliative measures do not exist
or are no longer effective.

- Ability to understand and the willingness to sign a written informed consent

- Patients must have at least one measurable lesion as per the RECIST Criteria that can
be accurately measured in at least one dimension, with minimum lesion size equal to
or more than twice the slice thickness of the imaging study used.

Exclusion Criteria:

- No symptomatic congestive heart failure

- No cardiac arrhythmia

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- 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)

- At least 2 weeks since prior radiotherapy

- Recovered from prior therapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other uncontrolled illness

- More than 2 weeks since prior valproic acid

- No other concurrent investigational drugs

- No other concurrent anticancer therapy

- Patients with known brain metastases are excluded from this clinical trial because of
their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximally tolerated dose of a combination of SAHA and gemcitabine determined by dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Gauri Varadhachary

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



M D Anderson Cancer Center Houston, Texas  77030