Papaverine Hydrochloride and Stereotactic Body Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of concurrent papaverine hydrochloride (PPV), and
lung SBRT in patients with non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To assess primary tumor control rate, local control rate, local-regional recurrence
free-survival (LRRFS), disease-free survival (DFS), distant-metastasis-free survival (DMFS),
and overall survival (OS).

II. To assess whether blood oxygen level-dependent (BOLD) functional magnetic resonance
imaging (MRI) studies can predict which patients may respond best to PPV + SBRT, and detect
changes in oxygenation before and after PPV administration.

III. To assess whether blood-based micro ribonucleic acid (miRNA) biomarkers can predict
which patients may respond best to PPV + SBRT.

OUTLINE: This is a dose-escalation study of papaverine hydrochloride.

Patients undergo BOLD functional magnetic resonance imaging (fMRI) and receive papaverine
hydrochloride intravenously (IV) on day 1. Within 30-90 minutes, patients undergo a second
BOLD fMRI. Patients then receive papaverine hydrochloride IV and within 30-90 minutes after
dose undergo SBRT for a up to 4-5 sessions over 2 weeks.

After completion of study treatment, patients are followed up at 4-6 weeks, 3 and 6 months, 1
and 2 years, then every 3 months for 2 years, and then every 6 months for 3 years.

Inclusion Criteria:

- Histologically or cytologically proven NSCLC for whom SBRT to a single lesion has been
chosen as the primary treatment modality (planned dose 50 Gy in 4-5 daily fractions)

- Patients must have a tumor =< 5 cm as defined by computed tomography (CT) largest
axial dimension. Presence of adjacent nodules considered neoplastic in the same lobe
or other ipsilateral lobe are allowed as long as the nodule(s) can be encompassed in
an SBRT gross tumor volume (GTV) of =< 5 cm, within 1 isocenter. Multiple isocenters
are not allowed

- No prior radiation resulting in overlapping fields

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Must be able to undergo correlative research MRIs

- No active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
(IPF)

- No history of complete atrioventricular block, hepatic dysfunction (e.g. cirrhosis),
glaucoma, or priapism

- Within 30 days of registration: patients must have vital signs, history/physical
examination, and laboratory studies (liver function tests, creatinine or creatinine
clearance assessment)

- Life expectancy of at least 12 weeks in the opinion of investigator

- Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14
days of registration. Urine human chorionic gonadotropin (HCG) is an acceptable
pregnancy assessment. Nursing women may participate only if nursing is discontinued,
due to the possibility of harm to nursing infants from the treatment regimen

- Within 90 days of registration: pulmonary function tests (PFTs) including forced
expiratory volume in 1 second (FEV-1) and diffusion capacity of the lung for carbon
monoxide (DLCO)

- Albumin >= 2.5 g/dL (within 30 days of study registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days of study
registration)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
(within 30 days of study registration)

- Creatinine =< 1.5 x ULN or calculated creatinine >= 50 mL/min, calculated by the
Cockcroft-Gault formula or 24-hour urine creatinine clearance >= 50 mL/min (within 30
days of study registration)

Exclusion Criteria:

- History of another malignancy

- Exception: Subjects who have been disease-free for >= 3 years, or subjects with a
history of localized prostate cancer, in situ carcinoma (e.g. breast, cervix,
oral cavity), differentiated thyroid neoplasm, completely resected non-melanoma
skin cancer, are eligible

- Any serious and/or unstable pre-existing medical disorder (aside from malignancy
exception above), psychiatric disorder, or other conditions that could interfere with
subject?s safety, obtaining informed consent or compliance to the study procedures, in
the opinion of the investigator

- Pregnancy or breastfeeding: Women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence) prior
to study entry, the duration of study participation and for 4 months after the last
dose of study treatment. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating physician
immediately. No breastfeeding while patient is on study

- Patients with history of pneumonectomy

- Prior cytotoxic chemotherapy, molecularly-targeted agents (e.g. erlotinib,
crizotinib), or immunotherapy unless >= 2 weeks from last dose

- History of active connective tissue disease (scleroderma), idiopathic pulmonary
fibrosis, pneumonitis

- Hepatic insufficiency resulting in jaundice and/or coagulation defects, or not meeting
laboratory values (albumin, total bilirubin, AST/ALT)