Virus Therapy for Extensive-Stage Small Cell Lung Cancer
Name of the Trial
Phase II Randomized Study of Seneca Valley Virus-001 (NTX-010) after Platinum-Based Chemotherapy in Patients with Extensive-Stage Small Cell Lung Cancer (NCCTG-N0923). See the protocol summary.
Dr. Julian Molina, North Central Cancer Treatment Group
Why This Trial Is Important
Lung cancer is the leading cause of cancer death in the United States. Although about 85 percent of lung cancer cases are non-small cell lung cancer, more than 30,000 people are diagnosed with small cell lung cancer each year in the United States. Small cell lung cancer is the most aggressive type of lung cancer, with 5-year survival rates ranging between 5 percent and 15 percent. The most important prognostic factor is the extent of disease, that is, whether it is limited stage or extensive stage. Unfortunately, about two-thirds of patients have extensive-stage diseaseat diagnosis.
Combination chemotherapy, in which a platinum drug is paired with one or two other drugs (often etoposide), is the cornerstone of treatment for patients with extensive-stage small cell lung cancer. Although many patients initially respond to treatment, the disease almost always returns. Consequently, the likelihood of long-term survival for these patients is exceptionally low. New treatment approaches are needed to improve long-term survival of patients with small cell lung cancer.
Seneca Valley virus-001 (also called NTX-010) is an oncolytic virus that was originally discovered as a contaminant in cell cultures. In preclinical experiments, the virus was found to readily infect, replicate in, and kill cancer cells with neuroendocrine features (including small cell carcinomas) but was not toxic to normal cells.
These studies led to a phase I dose-escalation trial in patients with small cell carcinomas and carcinoid tumors. The six patients in the study with small cell cancers (five of whom had small cell lung cancer) were all treated at the lowest dose, and a subsequent protocol change that limited enrollment to patients with a life expectancy of 6 months or longer precluded the enrollment of patients with recurrent small cell lung cancer in the higher dose groups. Nevertheless, the researchers found evidence of viral infection in three of the six patients with small cell cancer, including one who experienced stable disease for 10 months and was still alive more than 3 years after treatment.
In this clinical trial, patients with extensive-stage small cell lung cancer who have received platinum-based chemotherapy will be randomly assigned to receive Seneca Valley virus-001 intravenously or an intravenous placebo. Patients with previously untreated disease are eligible for the trial, but they must undergo four to six cycles of a platinum-based chemotherapy regimen and then be assessed for response. Patients with stable disease or a response will be randomly assigned to treatment or placebo. Patients participating in the study may also undergo two rounds of prophylactic cranial irradiation. The primary objective is to compare progression-free survival between the two groups. The investigators will also compare overall survival and assess adverse events, response rates, and quality of life.
“Our study is aimed at patients who have received first-line chemotherapy for extensive-stage small cell lung cancer; we’re randomizing them on a one-to-one basis to receive either the virus at the highest dose tested in the phase I study or a placebo,” said Dr. Molina. “It’s important that we compare the virus treatment to what you normally do for patients in this situation, which is nothing.”