Papaverine in Combination With Chemoradiation for the Treatment of Stage II-III Non-small Cell Lung Cancer

NCT05136846 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: OSU-20327NCI-2021-07691R01CA262388
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial finds out the best dose, possible benefits and/or side effects of papaverine when given together with chemoradiation intreating patients with stage II-III non-small cell lung cancer. Papaverine targets mitochondrial metabolism to decrease the cancer growth process. Giving papaverine with chemoradiation may work best to treat patients with non-small cell lung cancer.

Conditions

Locally Advanced Lung Non-Small Cell Carcinoma; Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximally tolerated dose (MTD) of papaverine (PPV) in combination with chemoradiation treatment (CRT) or definitive hypofractionated radiation therapy

  Will employ the Time-to-event Bayesian optimal interval design to find the MTD. Treatment-related toxicity will be assessed based on Common Terminology Criteria for Adverse Events version 5.0 criteria.

  6 weeks

Secondary Outcomes (9)

• Primary tumor control rate

  At 12 and 24 months post-treatment

• Local control rate

  At 12 and 24 months post-treatment

• Time to local-regional progression

  From entry on the study until the time of documented local-regional recurrence or death, assessed at 12 and 24 months post-treatment

• Disease-free survival

  From entry on the study until the time of any documented disease recurrence or death, assessed at 12 and 24 months post-treatment

• Distant-metastasis-free survival

  At 12 and 24 months post-treatment

Study Arms (1)

Treatment (papaverine, RT, paclitaxel, carboplatin)

EXPERIMENTAL

Patients receive PPV IV or SC over 30 minutes and patients receiving chemoradiation undergo 5 fractions of RT per week for 6 weeks or 5 fractions of hypofractionated RT per week for 3 weeks without chemotherapy. Patients undergoing chemoradiation receive paclitaxel IV and carboplatin IV QW over 1-6 weeks or pemetrexed IV followed by carboplatin IV every 3 weeks during radiation in the absence of disease progression or unacceptable toxicity. Patients with PD-L1 positive disease may also receive durvalumab after completing CRT as considered clinically appropriate by the treating medical oncologist. Patients also undergo PET/CT or CT and brain MRI during screening, and blood sample collection, MRI and CT scans throughout the trial.

Drug: Carboplatin; Biological: Durvalumab; Drug: Paclitaxel; Drug: Papaverine; Radiation: Radiation Therapy; Drug: Pemetrexed; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast; Procedure: Biospecimen Collection

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (papaverine, RT, paclitaxel, carboplatin)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (papaverine, RT, paclitaxel, carboplatin)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (papaverine, RT, paclitaxel, carboplatin)

Papaverine DRUG

Given IV or SC

Also known as: Cerebid, Cerespan, Pavabid, Pavacap, Pavatym, Robaxapap

Treatment (papaverine, RT, paclitaxel, carboplatin)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (papaverine, RT, paclitaxel, carboplatin)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Treatment (papaverine, RT, paclitaxel, carboplatin)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated RT

Also known as: Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation

Treatment (papaverine, RT, paclitaxel, carboplatin)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, nuclear magnetic resonance imaging, sMRI, Structural MRI

Treatment (papaverine, RT, paclitaxel, carboplatin)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, PET, Pet Scan, Positron emission tomography (procedure), positron emission tomography scan, Positron-Emission Tomography, PT

Treatment (papaverine, RT, paclitaxel, carboplatin)

Computed Tomography PROCEDURE

Undergo PET/CT or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT SCAN, tomography

Treatment (papaverine, RT, paclitaxel, carboplatin)

Magnetic Resonance Imaging of the Brain with and without Contrast PROCEDURE

Undergo brain MRI

Also known as: Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without Contrast

Treatment (papaverine, RT, paclitaxel, carboplatin)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (papaverine, RT, paclitaxel, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) =\< grade 1 (except alopecia) at the time of enrollment
• Absolute neutrophil count \>=1.5 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Creatinine \< 1.5 mg/dL or calculated creatinine clearance\* \>= 50 mL/min or 24-hour urine creatinine clearance \>= 50 mL/min
• Calculated by the Cockcroft-Gault formula •\>= 18 years old
• Non-small cell lung cancer (NSCLC), histologically and/or cytologically proven
• Clinical American Joint Committee on Cancer (AJCC) stage II-III NSCLC (T1-4N0-3M0) and select patients with stage IV oligometastatic disease.
• For patients with oligometastatic disease (up to 5 total sites of disease) for whom definitive CRT or RT to the primary and regional lymph nodes is recommended by the multidisciplinary team, each individual metastatic tumor would be considered an additional site of disease with the exception of brain metastases. Up to 10 brain metastases would be considered as 1 site.
• Patients with oligometastatic disease will be allowed to receive adjuvant systemic therapy at the discretion of the medical oncologist and additional local therapy to metastatic sites at the discretion of the multidisciplinary team
• Patients must be considered unresectable or medically-inoperable if stage II-III NSCLC
• Patients with a local or regional recurrence following surgical resection for whom definitive CRT or RT to disease in the chest is recommended by the multidisciplinary team will be considered eligible
• Patients must have fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)-computed tomography (CT) scan (or CT chest/abdomen/pelvis with IV contrast), and magnetic resonance imaging (MRI) brain with IV contrast (preferred) or CT scan of the brain with contrast. Non-contrast MRI scans of the chest/abdomen/pelvis or brain are permitted for workup if patient has allergy to CT contrast or renal insufficiency

You may not qualify if:

• Patients with history of pneumonectomy
• History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
• History of previous radiation therapy which would result in overlapping radiation fields
• Subjects who are breast-feeding and plan to continue breast-feeding during therapy, or have a positive pregnancy test will be excluded from the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Hepatic insufficiency resulting in jaundice, or not meeting laboratory values above (albumin, total bilirubin, AST/ALT)
• Patients enrolled into the expansion cohort must be able to complete the MRI Sub-study, or at a minimum attempt the first scan of the MRI Sub-study
• 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 treating physicians. This could include severe, active co-morbidities such as:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acquired immune deficiency syndrome (AIDS) based upon the current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
• Patients who are presently receiving nitrates or nitroglycerin, or have received these medications within 30 days of day 1 of protocol treatment
• Patients who are currently taking Sildenafil should agree to discontinue use for 2 days prior to initiation of papaverine, during the duration of study, and for 2 days after last dose of papaverine
• Any medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm clips, pregnancy, nursing mothers, weight greater than 350 pounds)
• Severe anxiety/claustrophobia related to MR imaging despite medications to relieve anxiety/claustrophobia

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; durvalumab; Immunoglobulin G; Disulfides; Paclitaxel; Taxes; Papaverine; Radiotherapy; Radiation; Pemetrexed; Radiation Dose Hypofractionation; Magnetic Resonance Spectroscopy; X-Rays; Contrast Media; Specimen Handling

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Opiate Alkaloids; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Physical Phenomena; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Dose Fractionation, Radiation; Radiotherapy Dosage; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Radiation, Ionizing; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Jeremey Brownstein, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: November 29, 2021
• Study Start: December 6, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)