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

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ClinicalTrials.gov Identifier: NCT03824327
Recruitment Status : Recruiting
First Posted : January 31, 2019
Last Update Posted : March 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Terence Williams, Ohio State University Comprehensive Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lung Non-Small Cell Carcinoma Procedure: Blood Oxygen Level Dependent Imaging Drug: Papaverine Hydrochloride Radiation: Stereotactic Body Radiation Therapy Phase 1

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial Combining Papaverine and Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer
Actual Study Start Date : February 7, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (BOLD fMRI, papaverine hydrochloride, SBRT)
Patients undergo BOLD fMRI and receive papaverine hydrochloride 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.
Procedure: Blood Oxygen Level Dependent Imaging
Undergo BOLD fMRI
Other Names:
  • Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging
  • BOLD
  • BOLD fMRI

Drug: Papaverine Hydrochloride
Given IV
Other Names:
  • Cerebid
  • Cerespan
  • Pap H
  • Pavabid
  • Pavacap
  • Therapav
  • Vasal
  • Vaso-Pav
  • Vasospan

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy




Primary Outcome Measures :
  1. Maximum-tolerated dose (MTD) [ Time Frame: Up to 2 weeks ]
    Will employ the Bayesian optimal interval (BOIN) design to find the MTD.


Secondary Outcome Measures :
  1. Primary tumor control [ Time Frame: At 12 and 24 months after stereotactic body radiation therapy (SBRT) completion ]
    Primary tumor control is defined as the absence of primary tumor failure. Will be calculated and 95% exact binomial confidence interval will be provided.

  2. Local control rate (primary tumor control + involved lobar control) [ Time Frame: Up to 12 months after SBRT completion ]
    Local control is defined as the absence of local failure. Will be calculated and 95% exact binomial confidence interval will be provided.

  3. Local-regional recurrence free-survival [ 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 ]
    Will be summarized using Kaplan-Meier method.

  4. Distant metastasis-free survival [ Time Frame: Time from entry onto study until the time of documented metastatic recurrence or death, assessed up to 12 months after SBRT treatment ]
    Will be summarized using Kaplan-Meier method.

  5. Disease-free survival [ 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 ]
    Will be summarized using Kaplan-Meier method.

  6. Overall survival [ Time Frame: Time from study entry until time of death from any cause, assessed up to 12 months after SBRT completion ]
    Will be summarized using Kaplan-Meier method.

  7. Changes in magnetic resonance imaging (MRI) blood oxygen level-dependent (BOLD) response [ Time Frame: Up to 4 hours ]
    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.

  8. Change in hypoxia-inducible micro ribonucleic acids (miRNAs) [ Time Frame: Up to 3 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03824327


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 1-800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Terence M. Williams    614-293-8415      
Principal Investigator: Terence M. Williams         
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Terence Williams, MD Ohio State University Comprehensive Cancer Center

Additional Information:
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Responsible Party: Terence Williams, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03824327     History of Changes
Other Study ID Numbers: OSU-18215
NCI-2019-00105 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA016058 ( U.S. NIH Grant/Contract )
First Posted: January 31, 2019    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Carcinoma, Bronchogenic
Respiratory Tract Diseases
Papaverine
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Urological Agents