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

Study Overview

• Status: Completed
• Conditions: Locally Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: vorinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vorinostat; Dose escalation of vorinostat, cisplatin, pemetrexed and radiation	Drug: vorinostat; vorinostat once daily for 12 weeks of therapy; Other Names: Zolinza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Comprehensive Cancer Network

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2009
• Primary Completion (Actual): July 22, 2015
• Study Completion (Actual): October 21, 2019

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: January 29, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: lung cancer; locally advanced lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: FER-TH-031; NCI-2010-01913 (Registry Identifier: NCI Clinical Trials Reporting Office)