Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase I Study of the HDAC Inhibitor Vorinostat With Chemotherapy and Radiation Therapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to determine the maximum tolerated dose of the combination of vorinostat, cisplatin, pemetrexed, and radiation therapy in patients with unresectable stage IIIA/IIIB non-small cell lung cancer.

This phase I trial will escalate doses of the histone deacetylase inhibitor (HDAC) vorinostat to a chemoradiation platform for cisplatin, pemetrexed and radiation to a dose of 70Gy in NSCLC patients with unresectable IIIA and dry IIIB disease. The endpoint will be to determine MTD of the combination.

Inclusion Criteria:

• biopsy proven non-squamous NSCLC with unresectable stage IIIA or dry IIIB disease.
• FEV1 >/= 1 liter
• ECOG PS 0 or 1
• Able to swallow and absorb enterally
• Measurable disease per RECIST 1.1
• Adequate organ and marrow function including calculated creatinine clearance >/= 60 mL/min hepatic enzymes and alk phos </= 2.5 X ULN.

Exclusion Criteria:

• Chemotherapy or radiotherapy </= 4 weeks prior to registration (6 weeks for nitrosureas)
• Active bleeding
• Known brain mets
• Prior thoracic radiotherapy that would lead to overlap with current radiation field.
• More than 10% weight loss in 6 months.
• Pancoast tumors, supraclavicular or contralateral hilar lymph node involvement
• Known HIV positive
• Prior treatment with an HDAC inhibitor