Trials / Terminated

TerminatedNCT02831933

Trial of Radiation and Gene Therapy Before Nivolumab for Metastatic Non-Small Cell Lung Carcinoma and Uveal Melanoma

ENSIGN: Phase II Window of Opportunity Trial of Stereotactic Body Radiation Therapy and In Situ Gene Therapy Followed by Nivolumab in Metastatic Squamous or Non-Squamous Non-Small Cell Lung Carcinoma and Metastatic Uveal Melanoma

Status: Terminated
Phase: Phase 2
Study type: Interventional
Enrollment: 11 (actual)

Sponsor: Eric Bernicker, MD · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

Detailed description

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 or non-squamous non-small cell lung carcinoma (NSCLC) and metastatic uveal melanoma. 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 whose disease has progressed after a platinum-based chemotherapy and a single-agent immunotherapy OR histologically or cytologically confirmed metastatic uveal melanoma that is immunotherapy naive are eligible to participate in the study. NSCLC 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 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 (480 mg) will be administered intravenously over 30 minutes every 4 weeks starting on day 17 of the study and continuing until disease progression, unacceptable toxicity, or up to 12 months in patients without disease progression. 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) clinical benefit rate (CBR); b) duration of response (DoR); c) overall survival (OS) and progression-free survival (PFS) rates; d) safety and toxicity (toxicity will be defined as any treatment-related death or any ≥ grade 3 toxicity excluding alopecia and constitutional symptoms as assessed by the NCI CTCAE v4.03); and e) 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.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	ADV/HSV-tk	Replication-defective recombinant adenovirus vector
DRUG	Valacyclovir	Prodrug of the antiviral drug acyclovir
RADIATION	SBRT	Low-dose SBRT
DRUG	nivolumab	Fully human immunoglobulin (Ig) G4 anti-PD-1 monoclonal antibody

Timeline

Start date: 2017-02-15
Primary completion: 2020-11-05
Completion: 2020-11-05
First posted: 2016-07-13
Last updated: 2023-09-21
Results posted: 2023-09-21

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02831933. Inclusion in this directory is not an endorsement.