This phase I trial studies the side effects and how well papaverine hydrochloride and stereotactic radiation therapy body (SBRT) work in treating patients with non-small cell lung cancer. Papaverine hydrochloride may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving papaverine hydrochloride with SBRT may work 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) or lung metastases. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Undergo BOLD fMRI
Given IV
Undergo SBRT
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Maximum-tolerated dose (MTD)
Will employ the Bayesian optimal interval (BOIN) design to find the MTD.
Time frame: Up to 2 weeks
Primary tumor control
Primary tumor control is defined as the absence of primary tumor failure. Will be calculated and 95% exact binomial confidence interval will be provided.
Time frame: At 12 and 24 months after stereotactic body radiation therapy (SBRT) completion
Local control rate (primary tumor control + involved lobar control)
Local control is defined as the absence of local failure. Will be calculated and 95% exact binomial confidence interval will be provided.
Time frame: Up to 12 months after SBRT completion
Local-regional recurrence free-survival
Will be summarized using Kaplan-Meier method.
Time frame: From time of entry onto study until the time of documented local-regional recurrence or death, assessed up to 12 months after SBRT completion
Distant metastasis-free survival
Will be summarized using Kaplan-Meier method.
Time frame: Time from entry onto study until the time of documented metastatic recurrence or death, assessed up to 12 months after SBRT treatment
Disease-free survival
Will be summarized using Kaplan-Meier method.
Time frame: Time from entry onto study until the time of any documented disease recurrence or death, assessed up to 12 months after SBRT completion
Overall survival
Will be summarized using Kaplan-Meier method.
Time frame: Time from study entry until time of death from any cause, assessed up to 12 months after SBRT completion
Changes in magnetic resonance imaging (MRI) blood oxygen level-dependent (BOLD) response
Will be measured before and after papaverine hydrochloride (PPV) delivery by the percentage change in relaxation rate on MRI. Will also analyze biomarkers descriptively and graphically to assess trends in changes in these markers over time and the association with response. Exploratory comparisons of groups of patients based on response will involve the use of analysis of variance (ANOVA) for continuous data and categorical methods such as Fisher?s exact and chi-square tests for discrete data.
Time frame: Up to 4 hours
Change in hypoxia-inducible micro ribonucleic acids (miRNAs)
Will analyze patient serum pre-and post-treatment for hypoxia-associated at pre- and post- SBRT treatment hypoxia-inducible microRNAs (miRs) using nanoString miRNA assay that could indicate the presence of tumor hypoxia. The changes in circulating biomarkers will be validated by alternative quantitative polymerase chain reaction (qPCR) based approaches. These results will be cross-validated with the BOLD data. Will also analyze biomarkers descriptively and graphically to assess trends in changes in these markers over time and the association with response. Exploratory comparisons of groups of patients based on response will involve the use of ANOVA for continuous data and categorical methods such as Fisher?s exact and chi-square tests for discrete data.
Time frame: Up to 3 months
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