Angiogenic Squamous Dysplasia Clinical Trial
Official title:
A Pilot Study of Oral Calcitriol in Patients at High Risk for Lung Cancer
This pilot clinical trial studies the side effects of calcitriol in preventing lung cancer in high risk patients. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of calcitriol may keep cancer from forming in patients with high risk for lung cancer.
| Status | Recruiting |
| Enrollment | 40 |
| Est. completion date | |
| Est. primary completion date | December 2017 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 40 Years to 79 Years |
| Eligibility |
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) |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Roswell Park Cancer Institute | National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of patients with grade III-IV toxicities or grade 2 toxicities that persist more than 2 weeks, graded according to the Common Terminology Criteria for Adverse Events 4.0 | Up to 30 days after completion of study treatment | Yes | |
| Secondary | Optimal biologic concentration, defined as the steady state concentration range that is associated with less than grade 2 toxicity and leads to target inhibition in 90% or greater of patients | The relationship between exposure levels (concentration in plasma or area under curve) of calcitriol with pharmacodynamic endpoints and polymorphisms in cytochrome P450 24A1 (CYP24A1) and calcitriol metabolizing enzymes will be examined. | Up to 3 months | No |
| Secondary | Pharmacokinetic/pharmacodynamic structural model for calcitriol, based on toxicity responses in previous trials | A variety of compartmental population pharmacokinetic structural models will be evaluated to characterize the serum concentration versus time profile following the oral administration of calcitriol. The physiologic pharmacokinetic models explored will be described by the estimation of mean structural model parameters (e.g., plasma volumes of distribution and clearances), the magnitude of inter-individual variability in these parameters, and the magnitude of residual variability. | Up to 3 months | No |