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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Locally Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: vorinostat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vorinostat<br>Dose escalation of vorinostat, cisplatin, pemetrexed and radiation | Drug: vorinostat<br>* vorinostat once daily for 12 weeks of therapy<br>* Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess that safety and maximally tolerated dose of vorinostat in combination with chemoradiation for unresectable locally advanced NSCLC. |  | toxicity assessments will occur weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate progression free survival. |  | CT/PET scans will be done after 12 weeks of therapy and at 12 week intervals until documented progression | 
| To evaluate response rates with this combination |  | CT/PET will be done following 12 weeks of therapy. | 
| To assess if pre-treatment tumor expression of TS, ERCC1 and HDAC1, 2, 3 are associated with response rate. |  | Archival tissue will be tested and correlated to response rates. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, locally advanced lung cancer