NCT03029871

Oncolytic Adenovirus-Mediated Gene Therapy for Lung Cancer

Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Combination With Stereotactic Body Radiation Therapy (SBRT) in Clinical Stage 1/11A (T1A-T2B) Non-Small Cell Lung Cancer

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Benjamin Movsas, M.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay the foundation for a follow-up phase 2 trial designed to examine efficacy.

Detailed description

Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring \> 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered \[18F\]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression. Toxicity assessments will occur twice a week for the first 2 weeks and then at scheduled follow-up visits through 60 months. The primary endpoint is toxicity. Secondary endpoints include 1) tumor (radiological) response, 2) local, regional, and distal tumor control, 3) progression-free and overall survival, and 4) quality of life. Exploratory endpoints include 1) intensity, persistence, and biodistribution of HSV-1 TK gene expression, and 2) association of select serum biomarkers with toxicity and tumor response.

Conditions

• Non-small Cell Lung Cancer Stage I

Interventions

Type	Name	Description
BIOLOGICAL	Ad5-yCD/mutTKSR39rep-ADP Adenovirus	oncolytic adenovirus

Timeline

• Start date: 2017-01-13
• Primary completion: 2018-12-31
• Completion: 2022-12-31
• First posted: 2017-01-24
• Last updated: 2019-08-13

Locations

1 site across 1 country: United States