Recruiting

Phase 1

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

Sponsor:

Ohio State University Comprehensive Cancer Center

Code:

NCT05136846

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Carboplatin

Durvalumab

Paclitaxel

Papaverine

Radiation Therapy

Study Details

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

Study ID

NCT05136846

Start date

Dec 6, 2021

Status verified date

Jun, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
Patients must have vital signs, history/physical examination, laboratory studies (complete blood count \[CBCP\] with differential, chemistries including liver function tests, creatinine clearance (CrCl) assessment; pregnancy test if needed within 14 days of registration)
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
No history of complete atrioventricular block, hepatic dysfunction (e.g. cirrhosis), glaucoma, or priapism
Patients must be a minimum of 3 weeks from thoracotomy (if performed) and well-healed before starting treatment
Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
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
Women/men of reproductive potential must be counselled on contraception/ abstinence while receiving the study treatment

Women of childbearing potential are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and until 6 months after the last dose of radiation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of study drug administration
For patients planning to undergo CRT, patient is suitable to receive standard chemotherapy per treating medical oncologist with radiation during study treatment

INCLUSION CRITERIA FOR MRI IMAGING SUB-STUDY:

•Patients must consent to participate in the main part of this study and be enrolled into the expansion cohort, or consent to participate in the main part of this study and also consent to participate in the optional MRI Imaging study

Exclusion Criteria:

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

EXCLUSION CRITERIA FOR MRI IMAGING SUB-STUDY:

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
Patients who use supplemental oxygen and are not able to stop their oxygen for up to a few hours at a time, or who use oxygen because they have breathing when they are laying down

Study Design

Enrollment

28 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (papaverine, RT, paclitaxel, carboplatin)

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.

Interventions

Carboplatin

Given IV

Durvalumab

Given IV

Paclitaxel

Given IV

Papaverine

Given IV or SC

Radiation Therapy

Undergo RT

Pemetrexed

Given IV

Hypofractionated Radiation Therapy

Undergo hypofractionated RT

Magnetic Resonance Imaging

Undergo MRI

Positron Emission Tomography

Undergo PET/CT

Computed Tomography

Undergo PET/CT or CT

Magnetic Resonance Imaging of the Brain with and without Contrast

Undergo brain MRI

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

Maximally tolerated dose (MTD) of papaverine (PPV) in combination with chemoradiation treatment (CRT) or definitive hypofractionated radiation therapy [ Time Frame: 6 weeks ]

Central Contacts and Locations

Central contacts

The Ohio State University Comprehensive Cancer Center

800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

Contacts

Terrence Williams, MD

626-218-5677 terwilliams@coh.org

Principal Investigator:

Terrence Williams, MD

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Jeremy M. Brownstein, MD

Jeremy.Brownstein@osumc.edu

Principal Investigator:

Jeremy Brownstein, MD

More Information

Sponsor

Ohio State University Comprehensive Cancer Center

Last update posted

Jun 30, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Ohio State University Comprehensive Cancer Center on 2026-06-30.