Calcitriol in Preventing Lung Cancer in High-Risk Patients

PRIMARY OBJECTIVES:

I. To establish the safety of 45 mcg dose of oral calcitriol every other week (QOW) in
non-cancer patients.

OUTLINE:

Patients receive calcitriol orally (PO) QOW on days 1 and 15. Treatment repeats every 28
days for up to 3 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Must have pathologically confirmed squamous metaplasia or squamous dysplasia
documented by autofluorescence bronchoscopy within the preceding 60 months

- Must be a former or current smoker

- Total granulocyte count of > 1.5 x 10^9/L

- Platelet count of > 100 x 10^9/L

- Participants must have adequate renal function with a calculated creatinine clearance
of > 60 ml/min from a serum specimen collection at baseline using the Cockcroft-Gault
formula

- Participants must have a 24-hour calcium concentration that is =< 300 mg/24 hours as
measured by 24-hour urine collection at baseline

- Total bilirubin less than the upper limit of normal

- Transaminases =< 2.5 x institutional upper limit of normal (IULN)

- Alkaline phosphatase =< 2.5 x IULN

- Albumin of >= 2.5 g/dl

- Participants must have an ionized serum calcium within normal limits

- Must meet Eastern Cooperative Oncology Group (ECOG) performance status criteria of
0-1 (0 = fully active, must be able to carry out all pre-disease activities without
restriction; 1 = restricted in physically strenuous activity, but ambulatory and able
to carry out work of a light or sedentary nature)

- Must be willing to attend all scheduled study visits, complete all study
questionnaires, and allow biological specimen collection including a bronchoscopy
within 3-4 months after enrollment into the study

- Women of child-bearing potential (i.e. women who are pre-menopausal or not surgically
sterile) must use acceptable contraceptive methods (abstinence, intrauterine device
[IUD], oral contraceptives or double barrier device) and must have a negative serum
or urine pregnancy test within 1 week prior to beginning treatment on this trial;
sexually active men must also use acceptable contraceptive methods; pregnant or
nursing patients are excluded from participating in this trial; contraceptive use
needs to be continued at least 1 month after the trial has ended

- Must be able and willing to sign an informed consent approved by the Institutional
Review Board (IRB)

Exclusion Criteria:

- Subjects with life-threatening medical conditions that would preclude bronchoscopy,
including: acute cardiac failure, which is unstable despite medication use;
uncontrolled hypertension; uncontrolled diabetes mellitus; or unstable coronary
artery disease

- Patients with severe metabolic disorders that would preclude administration of
calcitriol

- Evidence of current disease with lung cancer or head and neck cancer

- Patients may have a prior history of lung cancer or head and neck cancer treated with
curative intent, provided that there has been no evidence of disease (NED) for > 1
year; the qualifying autofluorescence (AF) bronchoscopy must be negative for
malignancy

- Patients with a history of any other malignancy within 3 years except non-melanoma
skin and cervical carcinoma in situ (CIS)

- Patients with a history of renal lithiasis within the last 5 years or patients with
evidence of kidney stones on entry evaluation

- Patients with impaired renal function creatinine clearance (CRCL) =< 60 mL/min

- Patients with hypercalcemia (using ionized calcium)

- Subjects taking calcium supplements; if subjects are willing to discontinue these
supplements, there must be a 2-month wash out period before enrollment

- If patients are routinely taking a multivitamin supplement, they will be asked to
continue the supplement as long as the amount of vitamin D in the supplement is not
in excess of the RDA (recommended daily allowance); if they are not taking a
multivitamin supplement, they will be asked to not start supplementation while on
study

- Subjects with a known hypersensitivity to calcitriol

- Subjects taking thiazides (which can decrease urinary excretion of calcium)

- Patients taking phenobarbital, digitalis, thiazides or ketoconazole

- Patients taking digoxin or patients who are susceptible to calcium-related
dysrhythmias

- Patients taking bile acid binding drugs (such as cholestyramine and colestipol)

- Patients taking danazol

- Patients taking aluminum-based antacids

- Oral ketoconazole or other azole antifungals

- Women who are pregnant or lactating are excluded from the study

- No known allergies to tree nuts (i.e. almonds)