Phase I Vorinostat Concurrent With Stereotactic Radiosurgery (SRS) in Brain Metastases From Non-Small Cell Lung Cancer

• The maximum tolerated dose of vorinostat with concurrent radiosurgery will be determined. [ Time Frame: 30 days following Stereotactic Radiosurgery ] [ Designated as safety issue: Yes ]
• During the expanded phase I portion of the study, the safety of the Maximum tolerated dose dose will be confirmed. [ Time Frame: 30 days following Stereotactic Radiosurgery ] [ Designated as safety issue: Yes ]
• he radiologic response, defined as local control and distant intra-cranial control rates at 3-months following radiotherapy, will be determined. [ Time Frame: 3 months following Stereotactic Radiosurgery ] [ Designated as safety issue: No ]

• The MTD and DLT of daily vorinostat concurrent with SRS will be determined.
• The safety of the MTD of vorinostat concurrent with radiotherapy will be confirmed.
• The radiologic response, defined as local control and distant intra-cranial control rates at 3-months following radiotherapy, will be determined.

• The short-term (< 30 days post-treatment) and long-term (> 30 days post-treatment) adverse effects will be determined. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• The 12-month survival rate from the date of Stereotactic Radiosurgery will be determined. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

• The short-term (< 30 days post-treatment) and long-term (> 30 days post-treatment) adverse effects will be determined.
• The 12-month survival rate from the date of SRS will be determined.

The purpose of this study is to determine the maximum tolerated dose (MTD) of vorinostat given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLCA) brain metastases in patient with 1-4 lesions.

• Brain Cancer
• Neoplasm Metastasis
• Lung Cancer
• Carcinoma, Non-Small-Cell Lung

• Drug: Vorinostat
  Orally up to 400 mg
• Procedure: Radiation Therapy
  Single fraction stereotactic radiotherapy - Standard of Care

Inclusion Criteria:- All patients age 18 years and older with histologically proven non-small cell lung cancer and 1-4 brain metastases, each measuring less than 2 cm will be eligible. Prior surgery or radiation is allowed as long as the target metastatic lesion(s) has not been treated with previous radiation.

• Adequate organ function (section 3.1.10).
• ECOG performance status 0-2.
• Life expectancy of >=12 weeks.
• Systemic chemotherapy washout period >=7 days.

Exclusion Criteria:Patients who have previously been treated with whole brain irradiation, pediatric patients (age <18), pregnant women, and patients who are unable to give informed consent.