NCT05136846

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: Ohio State University Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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.

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

Interventions

Type	Name	Description
DRUG	Carboplatin	Given IV
BIOLOGICAL	Durvalumab	Given IV
DRUG	Paclitaxel	Given IV
DRUG	Papaverine	Given IV or SC
RADIATION	Radiation Therapy	Undergo RT
DRUG	Pemetrexed	Given IV
RADIATION	Hypofractionated Radiation Therapy	Undergo hypofractionated RT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
PROCEDURE	Computed Tomography	Undergo PET/CT or CT
PROCEDURE	Magnetic Resonance Imaging of the Brain with and without Contrast	Undergo brain MRI
PROCEDURE	Biospecimen Collection	Undergo blood sample collection

Timeline

• Start date: 2021-12-06
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2021-11-29
• Last updated: 2025-06-04

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study