Status:
ACTIVE_NOT_RECRUITING
Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers
Lead Sponsor:
University of Colorado, Denver
Collaborating Sponsors:
Bristol-Myers Squibb
Conditions:
Bronchial Dysplasia
Tobacco Smoking
Eligibility:
All Genders
18-80 years
Phase:
PHASE2
Brief Summary
The goal of this clinical research study is to determine whether the PD-1 inhibitor (Programmed cell death protein 1) nivolumab improves premalignant bronchial dysplastic lesions in subjects that are ...
Detailed Description
This is a single-institution, open-label, single-arm, two-stage, phase II study of the PD-1 inhibitor nivolumab in patients at high risk for lung cancer. Simon's two-stage design will be used. In the ...
Eligibility Criteria
Inclusion
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged \> 18 years
- A current or ex-smoker with a \> 30 pack-year history of smoking and mild or worse sputum cytologic atypia or known bronchial dysplasia, OR history of non-small cell lung cancer (stage I, II, or IIIA) with \> 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment, OR history of head and neck cancer (stage I, II, III, or IVA) with \> 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment. An ex-smoker is defined as no tobacco use in the prior 12 months
- Endobronchial dysplasia (score \> 4) on screening bronchoscopy
- Total granulocyte count \> 1500
- Platelet count \> 100,000
- Serum creatinine \< 1.5 mg/dL
- Total bilirubin \< 2.0 mg/dL
- Transaminases and alkaline phosphatase \< 2.5x upper limit of normal
- Albumin \> 2.5 mg/dL
- ECOG performance status ≤ 1
- Participants must be able and willing to undergo three bronchoscopies: before, after four doses of nivolumab (8 weeks), and after 6 months
Exclusion
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Participants may not be currently receiving immune checkpoint inhibitor treatment or have been treated with immune checkpoint inhibitors in the past (including anti-programmed cell death receptor \[PD\]-1, anti-programmed death ligand 1 \[PD-L1\], and anti-cytotoxic T-lymphocyte associated protein 4 \[CTLA4\] monoclonal antibodies)
- Patients cannot receive any other investigational anti-cancer agents while participating in the study
- Participants cannot have used any other investigational agents within the previous six months
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
- Clinically apparent bleeding diathesis (i.e., bleeding that is spontaneous, excessive, or delayed in onset following tissue injury results from a localized pathologic process or a disorder of the hemostatic process, involving a complex interplay among vascular integrity, platelet number and function, coagulation factors, and fibrinolysis)
- Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (\< 2 minute) premature ventricular contractions are not exclusionary
- History of coronary artery disease, including myocardial infarction, congestive heart failure (LV ejection fraction \<50% or clinically significant diastolic dysfunction), or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study
- Individuals who are HIV-positive will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by the study investigators
- History of hepatitis B or hepatitis C infection that is untreated and/or with a detectable viral load
- Hypoxemia (less than 90% saturation with supplemental oxygen)
- Severe obstructive lung disease (GOLD Stage III or IV, FEV1\<30% predicted)
- Prior chemotherapy or thoracic radiation within the past 1 year
- Participants with findings on CT chest suspicious for lung cancer (Lung-RADS category 4) will not be allowed to enroll until they have undergone additional evaluation for malignancy and an alternative (i.e., non-malignant) diagnosis has been established
- Current malignancy, with the exception of non-melanoma (i.e., basal cell or squamous cell) skin cancer. Patients with lung carcinoma in situ found during the study biopsy are also excluded.
- History of a malignancy except for adequately treated non-melanoma (i.e., basal cell or squamous cell) skin cancer or in situ cervical cancer for which the subject has not been disease-free for 5 years. Patients with a history of non-small cell lung cancer (stage I, II, or IIIA) or head and neck cancer (stage I, II, III, or IVA) must have no evidence of active disease at least 1 year after definitive treatment.
- History of stage IIIA NSCLC for which the only treatment was chemoradiation without surgery
- Known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism requiring hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll
- Conditions requiring systemic corticosteroids equivalent to \> 10 mg prednisone per day or other immunosuppressive medications within 2 weeks of enrollment
- Known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- History of interstitial pneumonitis requiring treatment with systemic corticosteroids or other immunosuppressive agents (e.g., mycophenolate, azathioprine)
- Life expectancy of \< 1 year
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 4 weeks prior to the start of nivolumab
- Women must not be breastfeeding
- Inability to give informed consent
- Pneumonia or acute bronchitis for at least 2 weeks prior to enrollment
Key Trial Info
Start Date :
January 30 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2026
Estimated Enrollment :
19 Patients enrolled
Trial Details
Trial ID
NCT03347838
Start Date
January 30 2019
End Date
December 31 2026
Last Update
December 12 2025
Active Locations (2)
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1
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States, 80045
2
Denver VA Hospital
Denver, Colorado, United States, 80220