A Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in Combination With Temozolomide in Patients With Malignant Gliomas

Inclusion Criteria:

- Patients who have progressed on temozolomide are ineligible

- Patients in part 1 of this study must meet the following requirements:

- Stable disease or progression after radiation therapy (except if they have
progressed on temozolomide therapy) OR recurrent disease after treatment for any
number of prior relapses

- Must have recovered from the toxic effects of prior therapy

- 28 days since prior investigational agent

- 28 days since prior cytotoxic therapy

- 23 days since prior temozolomide for patients on a standard regimen (i.e., 5
days every 28 days)

- 14 days since prior vincristine

- 42 days since prior nitrosoureas

- 21 days since prior procarbazine administration

- 7 days since prior non-cytotoxic agents (e.g., interferon, tamoxifen,
thalidomide, cis-retinoic acid, etc.) except as a radiosensitizer

- No patients who are known to be HIV positive and are receiving combination
antiretroviral therapy

- Histologically proven intracranial malignant glioma, including the following
subtypes:

- Glioblastoma multiforme

- Gliosarcoma

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Malignant astrocytoma NOS (not otherwise specified)

- Original histology of a low-grade glioma and a subsequent histological diagnosis
of a malignant glioma

- Patients who have recently undergone resection of recurrent or progressive disease
must meet the following conditions:

- Recovered from the effects of surgery

- Residual disease following resection is not mandated for eligibility into the
study

- Patients with prior therapy that included interstitial brachytherapy or stereotactic
radiosurgery must have confirmation of true progressive disease rather than radiation
necrosis by positron emission tomography or thallium scanning, MR spectroscopy or
surgical documentation of disease

- Patients in part 2 of this study must meet the following requirements:

- Stable disease after radiation therapy

- Concurrent temozolomide with radiation therapy or radiation therapy alone, is
the only prior therapy permitted

- No recurrent disease

- Must be willing to participate in the pharmacokinetic studies

- Life expectancy > 8 weeks

- Karnofsky performance status >= 60

- WBC > 3,000/mm^3

- Absolute neutrophil count > 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin > 10 g/dL (transfusion allowed)

- SGOT < 2 times upper limit of normal (ULN)

- Bilirubin < 2 times ULN

- Creatinine < 1.5 mg/dL

- Pregnant women are excluded

- Women of childbearing potential must have a negative pregnancy test

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for the duration of the study

- Breastfeeding should be discontinued

- Must not have any significant medical illnesses that in the investigator's opinion
cannot be adequately controlled with appropriate therapy or would compromise the
patient's ability to tolerate this therapy

- No history of any other cancer, except non-melanoma skin cancer or carcinoma in-situ
of the cervix, unless in complete remission and off of all therapy for that disease
for a minimum of 3 years

- Must not have active infection or serious intercurrent medical illness

- Must not have any disease that will obscure toxicity or dangerously alter drug
metabolism

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to vorinostat or other agents used in study

- At least 2 weeks since prior valproic acid

- At least 3 weeks since radiation therapy

- No other investigational agents

- No other anticancer therapy (including chemotherapy, radiation, hormonal treatment or
immunotherapy) of any kind is permitted during the study period

- No concurrent routine prophylactic use of filgrastim (G-CSF)