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
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
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.
OBJECTIVES:
Primary
Secondary
Exploratory
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.
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.
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of extensive-stage small cell lung cancer (SCLC)
Presence of ≥ 1 neuroendocrine marker (synaptophysin, chromogranin, or CD56) in tumor tissue
Achieved partial response (PR), complete response (CR), or stable disease (SD) ≤ 12 weeks of completing 4-6 courses of platinum-based chemotherapy regimen for extensive-stage SCLC
Patients with PR or SD must have measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm but < 10 cm by chest x-ray OR as ≥ 1.0 cm but < 10 cm by CT scan, CT component of a PET/CT scan, or MRI
Brain metastases allowed provided they have been stable for ≥ 4 weeks after completion of prior radiotherapy
PATIENT CHARACTERISTICS:
ECOG performance status 0 or 1
Life expectancy of ≥ 8 weeks
ANC ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal
AST ≤ 3 times ULN (≤ 5 times ULN if liver has tumor involvement)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use adequate contraception
Able to comply with study procedures to minimize virus exposure to others
Willing to provide required biologic specimens
Willing to return to NCCTG/CTSU enrolling institution for follow-up
Adequate lung function (i.e., not oxygen dependent)
No second primary malignancy within the past 5 years, except for the following:
No active hepatitis B or hepatitis C
No clinically significant infection
No significant traumatic injury within the past 4 weeks
No concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
More than 4 weeks since prior radiotherapy (2 weeks for palliative radiotherapy to skeletal metastases)
Other prior radiation therapy (including WBRT, PCI, or Gamma Knife) is permitted as long as the following are true:
More than 365 days since prior immunotherapy or biologic therapy
More than 4 weeks since prior major surgery* (i.e., laparotomy) or open biopsy
More than 2 weeks since prior minor surgery*
No prior exposure to the Seneca Valley virus (NTX-010), as determined by negative serum antibodies
No concurrent combination antiretroviral therapy for HIV-positive patients NOTE: *Insertion of a vascular access device is not considered major or minor surgery.
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