Calcitriol in Preventing Lung Cancer in Smokers and Former Smokers at High Risk of Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Calcitriol may prevent lung cancer in patients with metaplasia or dysplasia of the lungs. PURPOSE: This clinical trial is studying the side effects and best dose of calcitriol in preventing lung cancer in current smokers and former smokers at high risk of lung cancer.

Detailed Description
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OBJECTIVES: Primary To establish the safety of calcitriol in patients at high risk of lung cancer. To determine the dose-limiting toxicities of calcitriol in these patients. OUTLINE: Patients receive oral calcitriol on day 1. Courses repeat every 2 weeks for 3 months in absence of unacceptable toxicity. Patients undergo blood collection periodically for pharmacokinetic and molecular analysis. After completion of study therapy, patients are followed periodically.

Official Title
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A Pilot Study of Oral Calcitriol in Patients at High Risk for Lung Cancer

Conditions
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Lung Cancer, Precancerous Condition, Tobacco Use Disorder

Intervention / Treatment
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* Drug: calcitriol
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed squamous metaplasia or squamous dysplasia of the lungs by autofluorescence bronchoscopy within the past 5 years Must be a current or former smoker No evidence of concurrent disease with lung cancer or head and neck cancer History of treated lung cancer or head and neck cancer treated with curative intent allowed, provided that there has been no evidence of disease for > 1 year PATIENT CHARACTERISTICS: ECOG performance status 0-1 Total granulocyte count > 1,500 x 10^9cells/L Platelet count > 100,000 x 10^9cells/L Calculated Creatinine clearance > 60 mL/min (using the Cockcroft-Gault formula) Calcium concentration 50-300 mg/24 hours Total bilirubin 0.2-1.3 mg% ALT/AST ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Albumin ≥ 2.5 g/dL Ionized serum calcium normal (1.19-1.29 mmol/L) Corrected serum calcium ≤ 10.2 mg/dL Willing to attend all scheduled study visits, complete all study questionnaires, and allow biological specimen collection, including a bronchoscopy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 1 month after completion of study therapy No life-threatening medical conditions that would preclude bronchoscopy, including but not limited to, any of the following: Acute cardiac failure Uncontrolled hypertension Uncontrolled diabetes mellitus Unstable coronary artery disease No severe metabolic disorders that would preclude calcitriol administration No history of any other malignancy within 3 years except for nonmelanoma skin cancer or cervical carcinoma in situ No history or evidence of kidney stones No patients who are susceptible to calcium-related dysrhythmias No known hypersensitivity to calcitriol No known allergies to tree nuts (i.e., almonds) PRIOR CONCURRENT THERAPY: At least 2 months since prior and no concurrent calcium supplements Concurrent multivitamin supplement allowed provided the amount of vitamin D in the supplement is not in excess of the recommended daily dose No concurrent thiazides, phenobarbital, or digitalis No concurrent digoxin No concurrent bile acid binding drugs (i.e., cholestyramine, colestipol) No concurrent danazol or aluminum-based antacids No concurrent ketoconazole or other azole antifungals

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcitriol<br> | Drug: calcitriol<br>* Oral<br>Other: laboratory biomarker analysis<br>* Correlative Study<br>Other: pharmacological study<br>* Correlative Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade III-IV Toxicities or Any Grade II Toxicities Lasting More Than 2 Weeks | Number of participants with Adverse Events, Grade II lasting more than two weeks or Grade III or higher, graded according to CTEP Version 4 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) will be utilized for AE reporting. CTEP Version 4 of the CTCAE is identified and located at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, tobacco use disorder, squamous lung dysplasia