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This is a Phase II trial to determine the efficacy and safety of in situ gene therapy and stereotactic body radiation therapy (SBRT) used as a window of opportunity treatment before nivolumab in patients with metastatic squamous and non-squamous non-small cell lung carcinoma (NSCLC). In situ gene therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus Valacyclovir therapy.
This is a Phase II trial to determine the efficacy and safety of in situ gene therapy and stereotactic body radiation therapy (SBRT) used as a window of opportunity treatment before nivolumab in patients with metastatic squamous and non-squamous non-small cell lung carcinoma (NSCLC). In situ gene therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus Valacyclovir therapy. Male or female patients aged ≥18 years with histologically or cytologically confirmed metastatic squamous or non-squamous NSCLC who are ineligible for cisplatin-based chemotherapy or whose disease has progressed after treatment with at least one platinum-containing regimen and at least one additional systemic therapy are eligible to participate in the study. Patients with EGFR or ALK genomic tumor aberrations are eligible only if they have had disease progression on FDA-approved therapy for these aberrations. ADV/HSV-tk (5 x 1011 viral particles) in a 2-mL total volume will be injected intratumorally at 0.5 ml carrying 1.25 x 1011 viral particles in each of 4 tumor quadrants on day 0 of the study. Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days. Valacyclovir treatment will be administered 24 hours after the gene vector injection from day 1 to day 15 of the study. SBRT of 30 gray (Gy; 6 Gy X 5 fractions) will be administered over 2 weeks from day 2 to day 16 of the study. Nivolumab (3 mg/kg) will be administered intravenously over 60 minutes every 2 weeks starting on day 17 of the study and continuing until disease progression or unacceptable toxicity. The primary endpoint will be the objective response rate (ORR) of ADV/HSV-tk + Valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before nivolumab in patients with metastatic squamous or non-squamous NSCLC. Both RECIST 1.1 and modified immune-related response criteria (irRC; derived from RECIST 1.1) will be used to assess treatment response. Secondary endpoints will include a) duration of response (DoR); b) overall survival (OS) and progression-free survival (PFS) rates; c) safety and toxicity (toxicity will be defined as any treatment-related death or any ≥ grade 3 non-hematological toxicity excluding alopecia and constitutional symptoms as assessed by NCI CTCAE v4.03); and d) immune-mediated antitumor activity (assessed by RECIST 1.1 and modified irRC) of ADV/HSV-tk plus Valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before nivolumab.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Lung Squamous Cell Carcinoma Stage IV
ADV/HSV-tk, Valacyclovir, SBRT, nivolumab
Houston Methodist Hospital
Not yet recruiting
The Methodist Hospital System
Published on BioPortfolio: 2016-07-14T00:38:22-0400
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