Seneca Valley Virus-001 After Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer
RATIONALE: A virus called Seneca Valley virus-001 (NTX-010) may be able to kill tumor cells without damaging normal cells. It is not yet known whether NTX-010 is more effective than a placebo in treating small cell lung cancer.
PURPOSE: This randomized phase II trial is studying NTX-010 to see how well it works compared with a placebo when given after chemotherapy in treating patients with extensive-stage small cell lung cancer.
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||A Randomized Double-Blinded Phase II Study of NTX-010, a Replication-Competent Picornavirus, After Standard Platinum-Containing Cytoreductive Induction Chemotherapy in Patients With Extensive Stage Small Cell Lung Cancer|
- Progression-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Response rate (complete response and partial response) as assessed by RECIST criteria [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Time-to-disease progression [ Designated as safety issue: No ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Quality of life as assessed by the single-item Linear Analogue Self Assessment [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive a single dose of Seneca Valley virus-001 (NTX-010) IV over 1 hour on day 1.
Biological: Seneca Valley virus-001
Placebo Comparator: Arm II
Patients receive a single dose of placebo IV over 1 hour on day 1.
- To compare the progression-free survival (PFS) of patients with extensive-stage small cell lung cancer treated with Seneca Valley virus-001 (NTX-010) vs placebo.
- To compare the overall survival (OS) of patients treated with NTX-010 vs placebo.
- To describe the adverse events profile and safety of NTX-010 in this patient population.
- To determine the antitumor response rate, as assessed by RECIST criteria, and duration of tumor response in this patient population.
- To assess the quality of life of this patient population.
- To determine the relationship between the presence of neutralizing antibodies and PFS.
- To assess whether or not a slow viral clearance is associated with better response as determined by PFS.
- To determine any potential impact of the presence of one or several neuroendocrine markers in the tumor sample (synaptophysin, chromogranin, or CD56) on PFS and OS.
- To determine any potential relationship between presence of cell surface determinants of NTX-010 tropism in the tumor tissue and clinical outcomes such as improved PFS and OS.
- To determine any potential relationship between the loss of integrity of IFN signaling in the tumor tissue and clinical outcomes such as improved PFS and OS.
- To assess whether or not the presence of circulating tumor cells permissive to NTX-010 is associated with better clinical outcomes as determined by PFS and OS.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), tumor response to standard chemotherapy (partial response vs stable disease vs complete response), and time between completion of chemotherapy to randomization 1 month (≤1 month) vs 2 months (>1 month but ≤ 2 months) vs 3 months (> 2 months but ≤ 3 months). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive a single dose of Seneca Valley virus-001 (NTX-010) IV over 1 hour on day 1.
- Arm II: Patients receive a single dose of placebo IV over 1 hour on day 1. In both arms, patients may also undergo prophylactic cranial irradiation (PCI) daily on days 22-35 if they have not previously undergone PCI or whole-brain radiotherapy.
Quality of life is assessed at baseline and then periodically during the study.
Blood samples are collected periodically for viral clearance and antiviral neutralizing antibody levels, circulating tumor cells, and other biomarker laboratory studies.
After completion of study therapy, patients are followed up periodically for up to 5 years.