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

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00690924
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 115.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Precancerous Condition; Tobacco Use Disorder	Drug: calcitriol; Other: laboratory biomarker analysis; Other: pharmacological study	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Pilot Study of Oral Calcitriol in Patients at High Risk for Lung Cancer
• Actual Study Start Date: Jul 17, 2008
• Actual Primary Completion Date: Mar 7, 2017
• Actual Study Completion Date: Mar 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Calcitriol	Drug: calcitriol; Oral; Other: laboratory biomarker analysis; Correlative Study; Other: pharmacological study; Correlative Study

Outcome Measures

Primary Outcome Measures

1. Grade III-IV Toxicities or Any Grade II Toxicities Lasting More Than 2 Weeks [3 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mary Reid, PhD, Roswell Park Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 11, 2017

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00690924
• Other Study ID Numbers: CDR0000596506; P30CA016056; I 90206; NCT01896804
• First Posted: Jun 5, 2008
• Last Update Posted: Jun 4, 2018
• Last Verified: May 1, 2018

• Keywords provided by Roswell Park Cancer Institute: lung cancer; tobacco use disorder; squamous lung dysplasia
• Additional relevant MeSH terms: Lung Neoplasms; Precancerous Conditions; Tobacco Use Disorder; Calcitriol

Study Results

Participant Flow

Arm/Group Title	Calcitriol
Arm/Group Description	calcitriol: Oral laboratory biomarker analysis: Correlative Study pharmacological study: Correlative Study
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Calcitriol
Arm/Group Description	calcitriol: Oral laboratory biomarker analysis: Correlative Study pharmacological study: Correlative Study
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 75%
>=65 years	4 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (8.6)
Sex: Female, Male (Count of Participants)
Female	6 37.5%
Male	10 62.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	16 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Grade III-IV Toxicities or Any Grade II Toxicities Lasting More Than 2 Weeks
Description	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.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Calcitriol
Arm/Group Description	calcitriol: Oral laboratory biomarker analysis: Correlative Study pharmacological study: Correlative Study
Measure Participants	16
II	1 6.3%
III	0 0%
IV	0 0%
V	0 0%

Adverse Events

Time Frame	4 months
Arm/Group Title	Calcitriol
Arm/Group Description	calcitriol: Oral laboratory biomarker analysis: Correlative Study pharmacological study: Correlative Study
All Cause Mortality
	Calcitriol
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Serious Adverse Events
	Calcitriol
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Calcitriol
	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)
Blood and lymphatic system disorders
Anaemia	1/16 (6.3%)	1
Cardiac disorders
Arrhythmia	1/16 (6.3%)	1
Palpitations	1/16 (6.3%)	1
Eye disorders
Eyelid irritation	1/16 (6.3%)	1
Gastrointestinal disorders
Abdominal pain	1/16 (6.3%)	5
Constipation	2/16 (12.5%)	2
Dry mouth	1/16 (6.3%)	1
Nausea	1/16 (6.3%)	1
Vomiting	1/16 (6.3%)	1
General disorders
Chills	1/16 (6.3%)	1
Facial pain	1/16 (6.3%)	1
Fatigue	2/16 (12.5%)	2
Malaise	1/16 (6.3%)	1
Injury, poisoning and procedural complications
Tooth fracture	1/16 (6.3%)	1
Investigations
Aspartate aminotransferase increased	4/16 (25%)	5
Blood alkaline phosphatase increased	2/16 (12.5%)	2
Calcium ionised increased	2/16 (12.5%)	2
Metabolism and nutrition disorders
Dehydration	1/16 (6.3%)	1
Hypercalcaemia	7/16 (43.8%)	13
Hyperglycaemia	4/16 (25%)	7
Hyperkalaemia	2/16 (12.5%)	3
Hypernatraemia	2/16 (12.5%)	2
Hypoglycaemia	4/16 (25%)	6
Hyponatraemia	4/16 (25%)	4
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/16 (6.3%)	1
Nervous system disorders
Dizziness	1/16 (6.3%)	5
Headache	2/16 (12.5%)	3
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1
Dysphonia	1/16 (6.3%)	1
Dyspnoea	2/16 (12.5%)	2
Epistaxis	1/16 (6.3%)	1
Nasal congestion	1/16 (6.3%)	1
Oropharyngeal pain	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/16 (6.3%)	1
Vascular disorders
Hot flush	1/16 (6.3%)	1
Hypotension	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.