Lung Cancer Clinical Trial

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

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.

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Full Description

PRIMARY OBJECTIVE:

I. To determine the maximally tolerated dose of papaverine (PPV) in combination with chemoradiation (CRT) and immunotherapy in patients with unresectable locally advanced (LA) non-small cell lung cancer (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, 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) and undergo 5 fractions of radiation therapy (RT) per week. Patients also receive paclitaxel IV over 1 hour and carboplatin IV once weekly (QW) over 1-6 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 month of completing CRT, patients with PD-L1 positive disease receive durvalumab IV every 2 weeks (Q2W) for 12 months.

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.

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Eligibility Criteria

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
>= 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)
Patients must be considered unresectable or medically-inoperable
Within 60 days of registration: 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
Within 30 days of registration: patients must have vital signs, history/physical examination, laboratory studies (CBCP with differential, chemistries including liver function tests, creatinine clearance (CrCl) assessment; pregnancy test if needed within 14 days of registration)
Absolute neutrophil count >=1.5 x 10^9/L (within 30 days of study registration)
Hemoglobin >= 9 g/dL (within 30 days of study registration)
Platelets >= 100 x10^9/L (within 30 days of study registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days of study registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days of study registration)

Creatinine < 1.5 mg/dL or calculated creatinine clearance* >= 50 mL/min or 24-hour urine creatinine clearance >= 50 mL/min (within 30 days of study registration)

Calculated by the Cockcroft-Gault formula

If a pleural effusion is present and visible on both CT scan AND chest Xray, the investigator should exclude malignant disease by pleurocentesis to confirm cytologically-negative pleural fluid. If fluid is exudative or cytologically positive for tumor cells, patient is excluded

Patients with effusions that are minimal (i.e. not visible on chest x-ray) and that are too small to safely tap are eligible
Life expectancy of > 6 months in the opinion of investigator
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days of registration
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
Patient is suitable to receive standard chemotherapy with radiation during study treatment (i.e. carboplatin + paclitaxel)

Exclusion Criteria:

Documented or pathologically-proven metastatic disease
Presence of nodules considered neoplastic in contralateral lobes (M1a)
Patients with history of pneumonectomy
Prior cytotoxic chemotherapy or molecularly-targeted agents (e.g. erlotinib, crizotinib), unless > 2 years prior
Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy without evidence of disease for >= 3 years will be allowed to enter the trial
History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
History of previous radiation therapy which would result in overlapping radiation fields
Uncontrolled neuropathy grade 2 or greater, regardless of cause
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
If patient elects to have two research MRIs during dose-finding phase of trial, medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm clips, known contrast allergy to gadolinium contrast, pregnancy, nursing mothers, weight greater than 350 pounds) or severe anxiety/claustrophobia related to MR imaging despite medications to relieve anxiety/claustrophobia
Hepatic insufficiency resulting in jaundice and/or coagulation defects, or not meeting laboratory values above (albumin, total bilirubin, AST/ALT)

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
Hepatic insufficiency resulting in jaundice and/or coagulation defects

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

28

Study ID:

NCT05136846

Recruitment Status:

Recruiting

Sponsor:

Ohio State University Comprehensive Cancer Center

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There is 1 Location for this study

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Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States More Info
Jeremy M. Brownstein, MD
Contact
[email protected]
Jeremy Brownstein, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

28

Study ID:

NCT05136846

Recruitment Status:

Recruiting

Sponsor:


Ohio State University Comprehensive Cancer Center

How clear is this clinincal trial information?

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