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Phase I/II Calcitriol in Lung Cancer

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ClinicalTrials.gov Identifier: NCT00794547
Recruitment Status : Terminated
First Posted : November 20, 2008
Results First Posted : May 5, 2014
Last Update Posted : December 12, 2017
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Small Cell Lung Cancer
Intervention Drug: Calcitriol
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1 Phase 2
Hide Arm/Group Description

In the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose.

Calcitriol: Escalating dose of Calcitriol will be infused IV over 1 hour every 21 days.

In the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy.

Calcitriol: In this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy

Period Title: Overall Study
Started 18 16
Completed 18 16
Not Completed 0 0
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
Thirty-four patients were enrolled (18 in phase I and 16 in phase II).
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 34 participants
54
(34 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
22
  64.7%
Male
12
  35.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 34 participants
34
Histology   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Adenocarcinoma 21
Squamous carcinoma 12
NSCLC NOS 1
[1]
Measure Description: Tumor histology results. Categories include Adenocarcinoma, Squamous Carcinoma and Non-Small-Cell Lung Cancer Not Otherwise Specified (NSCLC NOS).
Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Performance Status 0 16
Performance Status 1 18
[1]
Measure Description: Eastern Cooperative Oncology Group Performance Status at baseline. Scores may be 0 (Asymptomatic; fully active, able to carry on all predisease activities without restriction) or 1 (Symptomatic but completely ambulatory; restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
Smoking Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Never Smoker 2
Ever Smoker 29
Unknown 3
1.Primary Outcome
Title MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Hide Description The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.
Time Frame 5 years
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Hide Analysis Population Description
Eighteen patients were enrolled, and 16 were evaluable for toxicity assessments. Two patients were not evaluable as they progressed prior to completion of cycle 1.
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description:
Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: mcg/m^2
60
2.Primary Outcome
Title Number of Participants That Experience Grade 3 or Greater Neutropenia
Hide Description The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.
Time Frame 30 days after last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Thirty-four patients were enrolled (18 in phase I and 16 in phase II). 16 of 18 patients enrolled in the Phase 1 portion of the study were evaluable for toxicity. One patient in the phase II study went to another therapy prior to the 30 day window for a confirmatory scan and was thus excluded from analysis.
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description:
Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
# of Phase 1 Participants w/ Grade 3+ Neutropenia 8
# of Phase 2 Participants w/ Grade 3+ Neutropenia 9
3.Primary Outcome
Title Median Time to Progression
Hide Description The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description:
Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
5.8
(3.4 to 6.5)
4.Primary Outcome
Title Median Overall Survival
Hide Description The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description:
Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
8.7
(7.6 to 39.4)
5.Secondary Outcome
Title Mean AUC 1,25-D3 Concentration at 12 and 24 Hours
Hide Description The mean AUC (area under the curve) concentrations of 1,25-D3 from 0-12 hours and 0-24 hours will be calculated.
Time Frame 12 and 24 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the phase II portion of the study were included in the pharmacokinetics analysis
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description:
Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Number of Participants Analyzed 16
Mean (Standard Error)
Unit of Measure: h*ng/mL
AUC 0-12 Hours 15.95  (0.92)
AUC 0-24 Hours 31.74  (1.92)
6.Other Pre-specified Outcome
Title To Correlate the Pharmacokinetic Parameters of Systemic Calcitriol Exposure (AUC) With SNPs of the 24-hydroxylase (CYP24), the Major Vitamin D3 Inactivating Enzyme.
Hide Description [Not Specified]
Time Frame 3-6 months
Outcome Measure Data Not Reported
Time Frame Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Calcitriol + Cisplatin + Docetaxel
Hide Arm/Group Description Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
All-Cause Mortality
Calcitriol + Cisplatin + Docetaxel
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Calcitriol + Cisplatin + Docetaxel
Affected / at Risk (%) # Events
Total   20/34 (58.82%)    
Blood and lymphatic system disorders   
Low Neutrophils/granulocytes (ANC/AGC)  2/34 (5.88%)  2
Cardiac disorders   
Supraventricular and nodal arrhythmia  2/34 (5.88%)  2
Hypotension  2/34 (5.88%)  2
Pain-Chest  1/34 (2.94%)  1
Gastrointestinal disorders   
Abdominal Pain  1/34 (2.94%)  1
Colitis  1/34 (2.94%)  1
Dehydration  3/34 (8.82%)  3
Diarrhea  3/34 (8.82%)  3
Esophagitis  1/34 (2.94%)  1
Nausea  2/34 (5.88%)  2
Vomiting  2/34 (5.88%)  2
Infections and infestations   
Febrile neutropenia  3/34 (8.82%)  3
Lung Infection  2/34 (5.88%)  2
Upper Airway Infection  1/34 (2.94%)  1
Metabolism and nutrition disorders   
Calcium, serum-low (hypocalcemia)  1/34 (2.94%)  1
Glomerular filtration rate  1/34 (2.94%)  1
Glucose, serum-low (hypoglycemia)  1/34 (2.94%)  1
Phosphate, serum-low (hypophosphatemia)  1/34 (2.94%)  1
Sodium, serum-low (hyponatremia)  1/34 (2.94%)  1
Musculoskeletal and connective tissue disorders   
Pain-Back  1/34 (2.94%)  1
Nervous system disorders   
Syncope (fainting)  1/34 (2.94%)  1
Respiratory, thoracic and mediastinal disorders   
Hemorrhage, pulmonary/upper respiratory  1/34 (2.94%)  1
Dyspnea (shortness of breath)  1/34 (2.94%)  1
Vascular disorders   
Thrombosis/thrombus/embolism  1/34 (2.94%)  1
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Calcitriol + Cisplatin + Docetaxel
Affected / at Risk (%) # Events
Total   34/34 (100.00%)    
Blood and lymphatic system disorders   
Low Hemoglobin  14/34 (41.18%)  23
Low Leukocytes (total WBC)  14/34 (41.18%)  24
Lymphopenia  11/34 (32.35%)  24
Low Neutrophils/granulocytes (ANC/AGC)  14/34 (41.18%)  23
Low Platelets  8/34 (23.53%)  15
Cardiac disorders   
Atrial fibrillation  3/34 (8.82%)  5
Sinus tachycardia  4/34 (11.76%)  6
Hypertension  3/34 (8.82%)  3
Hypotension  7/34 (20.59%)  10
Chest Pain  3/34 (8.82%)  4
Ear and labyrinth disorders   
Tinnitus  4/34 (11.76%)  5
Eye disorders   
Vision-blurred vision  3/34 (8.82%)  3
Gastrointestinal disorders   
Anorexia  15/34 (44.12%)  17
Constipation  7/34 (20.59%)  7
Dehydration  6/34 (17.65%)  10
Diarrhea  10/34 (29.41%)  15
Dysphagia (difficulty swallowing)  3/34 (8.82%)  4
Mucositis/stomatitis  7/34 (20.59%)  7
Nausea  21/34 (61.76%)  29
Taste alteration (dysgeusia)  9/34 (26.47%)  13
Vomiting  12/34 (35.29%)  16
Abdominal Pain  6/34 (17.65%)  10
Throat Pain  5/34 (14.71%)  5
General disorders   
Fatigue  17/34 (50.00%)  28
Fever  3/34 (8.82%)  3
Rigors/chills  4/34 (11.76%)  4
Edema: limb  4/34 (11.76%)  7
Pain NOS  3/34 (8.82%)  3
Infections and infestations   
Febrile neutropenia  4/34 (11.76%)  4
Investigations   
Weight loss  4/34 (11.76%)  7
Metabolism and nutrition disorders   
Elevated ALT, SGPT (serum glutamic pyruvic transaminase)  5/34 (14.71%)  15
Elevated AST, SGOT(serum glutamic oxaloacetic transaminase)  9/34 (26.47%)  13
Albumin, serum-low (hypoalbuminemia)  11/34 (32.35%)  15
Elevated Alkaline phosphatase  7/34 (20.59%)  12
Bilirubin (hyperbilirubinemia)  4/34 (11.76%)  5
Calcium, serum-low (hypocalcemia)  7/34 (20.59%)  11
Elevated Creatinine  4/34 (11.76%)  6
Glucose, serum-high (hyperglycemia)  17/34 (50.00%)  42
Phosphate, serum-low (hypophosphatemia)  4/34 (11.76%)  6
Potassium, serum-high (hyperkalemia)  6/34 (17.65%)  6
Potassium, serum-low (hypokalemia)  6/34 (17.65%)  8
Sodium, serum-low (hyponatremia)  14/34 (41.18%)  20
Musculoskeletal and connective tissue disorders   
Muscle weakness  5/34 (14.71%)  6
Back Pain  7/34 (20.59%)  10
Bone Pain  3/34 (8.82%)  3
Limb Pain  3/34 (8.82%)  4
Nervous system disorders   
Dizziness  7/34 (20.59%)  8
Neuropathy: sensory  4/34 (11.76%)  5
Head Pain  5/34 (14.71%)  6
Psychiatric disorders   
Insomnia  3/34 (8.82%)  5
Renal and urinary disorders   
Urinary retention  3/34 (8.82%)  3
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  4/34 (11.76%)  5
Bronchospasm, wheezing  3/34 (8.82%)  3
Cough  9/34 (26.47%)  11
Dyspnea  8/34 (23.53%)  14
Skin and subcutaneous tissue disorders   
Hair loss/alopecia (scalp or body)  5/34 (14.71%)  5
Rash/desquamation  7/34 (20.59%)  7
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Nithya Ramnath
Organization: University of Michigan Comprehensive Cancer Center
Phone: 734-647-1417
EMail: nithyar@umich.edu
Layout table for additonal information
Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT00794547     History of Changes
Obsolete Identifiers: NCT00470431
Other Study ID Numbers: UMCC 2008.042
HUM 21242 ( Other Identifier: University of Michigan Medical IRB )
First Submitted: November 19, 2008
First Posted: November 20, 2008
Results First Submitted: March 31, 2014
Results First Posted: May 5, 2014
Last Update Posted: December 12, 2017