Clinical trial NCT01059552: Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Official title: Phase I Study of the HDAC Inhibitor Vorinostat With Chemotherapy and Radiation Therapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Non-small Cell Lung Cancer
Keywords: lung cancer
locally advanced lung cancer
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2010-02-01
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To assess that safety and maximally tolerated dose of vorinostat in combination with chemoradiation for unresectable locally advanced NSCLC.
timeFrame: toxicity assessments will occur weekly
Secondary outcomes:
measure: To investigate progression free survival.
timeFrame: CT/PET scans will be done after 12 weeks of therapy and at 12 week intervals until documented progression
measure: To evaluate response rates with this combination
timeFrame: CT/PET will be done following 12 weeks of therapy.
measure: To assess if pre-treatment tumor expression of TS, ERCC1 and HDAC1, 2, 3 are associated with response rate.
timeFrame: Archival tissue will be tested and correlated to response rates.
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Fox Chase Cancer Center
name: Ranee Mehra, MD
role: PRINCIPAL_INVESTIGATOR
References: