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Locally Advanced Lung Non-Small Cell CarcinomaPhase 1NCT05136846

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

A Phase 1 study testing Carboplatin, Durvalumab and Paclitaxel in people with Locally Advanced Lung Non-Small Cell Carcinoma and Stage II Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Durvalumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
2 sitesUnited States
Study dates
6 Dec 2021to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • •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

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

United States2 sites, 2 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Jeremy M. Brownstein, MD, Jeremy.Brownstein@osumc.edu

    Jeremy Brownstein, MD

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Terrence Williams, MD, 626-218-5677, terwilliams@coh.org

    Terrence Williams, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase I Trial Targeting Mitochondrial Metabolism With Papaverine in Combination With Chemoradiation for Stage II-III Non-Small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the maximally tolerated dose of papaverine (PPV) in combination with chemoradiation (CRT)/radiation therapy (RT) in patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) or oligometastatic NSCLC.

SECONDARY OBJECTIVES:

  1. To estimate the rates of primary tumor control, local control, time to local-regional progression, disease-free survival (DFS), and overall survival (OS). II. To assess whether blood oxygen level determination (BOLD) functional magnetic resonance imaging (MRI) studies can predict which patients may respond best to PPV + CRT/RT, and detect changes in oxygenation before and after PPV administration.

III. To assess whether blood-based and tissue-based biomarkers can predict which patients may respond best to PPV + CRT.

OUTLINE: This is a dose-escalation study of PPV.

Patients receive PPV intravenously (IV) or subcutaneously (SC) over 30 minutes and patients receiving chemoradiation undergo 5 fractions of radiation therapy (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 once weekly (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 positron emission tomography/computed tomography (PET/CT) or CT and brain magnetic resonance imaging (MRI) during screening, and blood sample collection, MRI and CT scans throughout the trial.

After completion of the study treatment, patients are followed for 2 years at 1, 3, 6, 9, 12, 16, 20, and 24 months, then periodically for up to 5 years.

Being tested
Carboplatin, Durvalumab, Paclitaxel, Papaverine, Radiation Therapy
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • DurvalumabBiological

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

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • PapaverineDrug

    Also called Cerebid, Cerespan, Pavabid, Pavacap

    Given IV or SC

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated

    Undergo RT

  • PemetrexedDrug

    Also called MTA, Multitargeted Antifolate, Pemfexy

    Given IV

  • Hypofractionated Radiation TherapyRadiation

    Also called Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation

    Undergo hypofractionated RT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, PET, Pet Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography

    Undergo PET/CT or CT

  • Magnetic Resonance Imaging of the Brain with and without ContrastProcedure or surgery

    Also called Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without Contrast

    Undergo brain MRI

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

Study groups in NCT05136846
Study groupRoleWhat they receive
Treatment (papaverine, RT, paclitaxel, carboplatin)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 weeks

Secondary outcomes (9)

  1. Primary tumor control rate

    Defined as the absence of primary tumor failure. Will be calculated and 95% exact binomial confidence interval will be provided.

    Measured: At 12 and 24 months post-treatment

  2. Local control rate

    Defined as the absence of local failure, which is a combination of primary tumor and involved lobe failure. Will be calculated and 95% exact binomial confidence interval will be provided.

    Measured: At 12 and 24 months post-treatment

  3. Time to local-regional progression

    Will be summarized using Kaplan-Meier method.

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

  4. Disease-free survival

    Will be summarized using Kaplan-Meier method.

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

  5. Distant-metastasis-free survival

    Will be summarized using Kaplan-Meier method.

    Measured: At 12 and 24 months post-treatment

  6. Overall survival

    Will be summarized using Kaplan-Meier method.

    Measured: From study entry until the time of death from any cause, assessed at 12 and 24 months post-treatment

  7. Changes in magnetic resonance imaging (MRI) blood oxygen level dependent (BOLD) response on MRI

    Images pre and post PPV will be analyzed for stability of baseline and treatment signals. Percent BOLD change will be determined for maximal and overall signal changes. Comparisons between the distributions of pre and post PPV will be valuated using Earth Mover's Distance.

    Measured: Baseline up to 24 months

  8. Changes in blood-based biomarkers related to predict patients response to PPV + CRT

    Will acquire measurements of circulating serum microRNAs that can indicate tumor hypoxia or response to therapeutic intervention, and alterations in immune cell subsets that are suggestive of immune system activation or suppression with the experimental therapy

    Measured: Baseline up to 24 months

  9. Changes in tissue-based biomarkers related to predict patients response to PPV + CRT

    When biopsy tissue is available, will acquire gene expression profiles by Affymetrix gene chip for indications of tumor hypoxia or response to therapeutic intervention, and correlating tumor mutations in genes involved in the anti-oxidant response pathway with outcomes.

    Measured: Baseline up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2021
  2. Study start6 Dec 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05136846
Sponsor's protocol ID
OSU-20327
Other IDs
NCI-2021-07691, R01CA262388
Status last verified
Jun 2026
First submitted
17 Aug 2021
Last updated
30 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carboplatin, Durvalumab and Paclitaxel in people with Locally Advanced Lung Non-Small Cell Carcinoma and Stage II Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05136846.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.

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