Actively Recruiting

Phase 1
Age: 18Years +
All Genders
ID05136846

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

Led by Ohio State University Comprehensive Cancer Center ยท Updated on 2025-06-04

28

Participants Needed

2

Research Sites

N/A

Total Duration

On this page

Sponsors

O

Ohio State University Comprehensive Cancer Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating papaverine in combination with chemoradiation or radiation therapy for patients with stage II-III non-small cell lung cancer (NSCLC) or selected stage IV oligometastatic NSCLC. This phase I trial aims to find the best dose of papaverine, a drug targeting mitochondrial metabolism to slow cancer growth, and to assess its possible benefits and side effects. The study also explores whether imaging and blood or tissue biomarkers can predict patient responses to the treatment. Participants receive papaverine intravenously or subcutaneously over 30 minutes alongside chemoradiation consisting of radiation therapy five times a week for 6 weeks or hypofractionated radiation therapy for 3 weeks without chemotherapy. Chemoradiation includes weekly paclitaxel and carboplatin or pemetrexed with carboplatin every 3 weeks during radiation. Patients with PD-L1 positive disease may also receive durvalumab after completing chemoradiation, based on clinical judgment. Imaging scans such as PET/CT, brain MRI, and blood sample collections are performed during screening and throughout the trial. During the study, participants undergo regular assessments including vital signs, physical exams, laboratory tests, and various imaging studies to monitor tumor control, disease progression, survival, and changes in oxygen levels and biomarkers. After treatment, follow-up visits occur at multiple intervals over 2 years and then periodically for up to 5 years to gather long-term data on outcomes and safety.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • All prior treatment-related toxicities must be mild or less (CTCAE grade 1 or lower, except alopecia) at enrollment
  • Absolute neutrophil count of at least 1.5 x 10^9/L
  • Hemoglobin level of at least 9 g/dL
  • Platelet count of at least 100 x 10^9/L
  • Total bilirubin no more than 1.5 times the upper limit of normal
  • AST and ALT levels no more than 2.5 times the upper limit of normal
  • Creatinine less than 1.5 mg/dL or creatinine clearance of at least 50 mL/min
  • Age 18 years or older
  • Histologically or cytologically confirmed non-small cell lung cancer
  • Clinical stage II-III NSCLC or selected stage IV oligometastatic disease with up to 5 total sites (brain metastases counted differently)
  • Considered unresectable or medically inoperable for stage II-III NSCLC
  • Completed PET/CT or CT chest/abdomen/pelvis with contrast, and brain MRI or CT with contrast
  • Vital signs, medical history, physical exam, and lab tests within 14 days prior to registration
  • ECOG performance status of 0 to 2
  • No history of complete atrioventricular block, severe liver disease, glaucoma, or priapism
  • At least 3 weeks since thoracotomy with well-healed surgical site
  • Able to provide written informed consent
  • Women of child-bearing potential must have a negative pregnancy test within 14 days
  • Nursing women must have stopped nursing
  • Women and men of reproductive potential must agree to use contraception during and after study treatment
  • Suitable to receive standard chemotherapy with radiation during study treatment
Not Eligible

You will not qualify if you...

  • History of pneumonectomy
  • Active connective tissue disease such as scleroderma or idiopathic pulmonary fibrosis
  • Prior radiation therapy overlapping with planned treatment fields
  • Currently breastfeeding or positive pregnancy test
  • Significant liver dysfunction causing jaundice or outside lab value limits
  • Unable to complete or attempt the MRI imaging sub-study if enrolled in expansion cohort
  • Serious or unstable medical or psychiatric disorders that interfere with safety or compliance
  • Unstable angina or heart failure requiring hospitalization in past 6 months
  • Recent transmural myocardial infarction within 6 months
  • AIDS diagnosis
  • Recent severe lung illness or COPD exacerbation requiring hospitalization within 30 days
  • Current use of nitrates or nitroglycerin within 30 days before treatment
  • Current use of sildenafil without agreement to discontinue before and during treatment
  • Contraindications to MRI such as pacemakers, metallic implants, severe anxiety, or oxygen dependency preventing MRI

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 screening and enrollment visit

Treatment

Duration - 3 to 6 weeks

Participants receive papaverine intravenously or subcutaneously in combination with chemoradiation or hypofractionated radiation therapy. Chemoradiation includes weekly paclitaxel and carboplatin over 1 to 6 weeks or pemetrexed followed by carboplatin every 3 weeks during radiation. Radiation therapy is given 5 times per week for 3 to 6 weeks. Participants with PD-L1 positive disease may receive durvalumab after completing chemoradiation as decided by their doctor.

Weekly visits during chemoradiation treatment

Follow-up

Duration - Up to 5 years

Participants are followed for up to 5 years after treatment completion to monitor tumor control, disease progression, survival, and changes in imaging and biomarkers.

Visits at 1, 3, 6, 9, 12, 16, 20, and 24 months, then periodically

Trial Site Locations

Total: 2 locations

1

City of Hope

Duarte, California, United States, 91010

Actively Recruiting

2

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

Actively Recruiting

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Research Team

T

The Ohio State University Comprehensive Cancer Center

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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