Seneca Valley Virus-001 After Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer

OBJECTIVES:

Primary

- 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.

Secondary

- 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.

Exploratory

- 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.

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of extensive-stage small cell lung cancer (SCLC)

- No mixed histology

- 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

- If CT scan is used, it must be used for both pre- and post-treatment tumor
assessments

- Measurable disease is not required for patients with CR

- 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)

- The patient is eligible if not on a 24-hour oxygen schedule

- No second primary malignancy within the past 5 years, except for the following:

- Carcinoma in situ of the cervix

- Non-melanomatous skin cancer

- History of low-grade (Gleason score ≤ 6) localized prostate cancer (even if
diagnosed < 5 years prior to study entry)

- Stage I breast cancer that was treated ≥ 5 years before study entry

- Transitional cell carcinoma of the bladder (in situ)

- 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:

- Recovered from prior radiotherapy (alopecia allowed)

- No prior consolidation radiation therapy to the chest

- No prior radiotherapy to > 25% of bone marrow

- For patients without brain metastases, WBRT or standard of care PCI completed ≥
2 weeks before administration of NTX- 010/placebo

- 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.