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Calcitriol in Combination With Ketoconazole and Therapeutic Hydrocortisone in Treating Patients With Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00536991
Recruitment Status : Terminated (difficult to recruit)
First Posted : September 28, 2007
Results First Posted : May 15, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Prostate Adenocarcinoma
Recurrent Prostate Carcinoma
Stage III Prostate Cancer
Stage IV Prostate Cancer
Interventions Dietary Supplement: Calcitriol
Drug: Ketoconazole
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Therapeutic Hydrocortisone
Enrollment 51
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
Period Title: Overall Study
Started 51
Completed 38
Not Completed 13
Reason Not Completed
Withdrawal by Subject             10
Physician Decision             1
patient ineligible             2
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
Overall Number of Baseline Participants 51
Hide Baseline Analysis Population Description
All treated and eligible patients
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants
<=18 years
0
   0.0%
Between 18 and 65 years
18
  35.3%
>=65 years
33
  64.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants
68.0  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants
Female
0
   0.0%
Male
51
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
6
  11.8%
White
45
  88.2%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Determine the Maximum Tolerated Dose (MTD)
Hide Description Determine the maximum tolerated dose (MTD) of oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole (400 mg thrice daily [TID]) + oral hydrocortisone (20 mg AM, 10 mg PM)
Time Frame up to 11 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Phase I participants
Arm/Group Title Treatment (Calcitriol, Ketoconazole, Hydrocortisone)
Hide Arm/Group Description:

PHASE I: Patients receive calcitriol PO QD on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO BID on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Calcitriol: Given PO

Ketoconazole: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Therapeutic Hydrocortisone: Given PO

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: mcg
10
2.Primary Outcome
Title PSA Response Rate
Hide Description Patients will be considered evaluable for PSA response if they have at least two post-baseline PSA measurements at least 4 weeks apart, or if they have other evidence of disease progression. A PSA response will be considered a PSA decline of at least 50% must be confirmed by a second PSA value four or more weeks later. The reference PSA for these declines should be a PSA measured within 2 weeks prior to the initiation of therapy.
Time Frame Up to 11 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description:
oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
Overall Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
35
(22 to 50)
3.Secondary Outcome
Title Incidence of Toxicity Graded According to the National Cancer Institute CTC Version 3.0
Hide Description Count of participants with serious adverse event. Please refer to the adverse event reporting for more detail.
Time Frame Up to 11 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description:
oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
14
  27.5%
4.Secondary Outcome
Title Objective Tumor Response, Assessed by RECIST
Hide Description Judged by monthly physical exam and radiographic evaluation. Patients will be considered evaluable for tumor response if they have at least two post-baseline tumor assessments at least 4 weeks apart, received study medication for 8 weeks or if they have evidence of disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame Up to 11 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients. 26 patients were not evaluable.
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description:
oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
Overall Number of Participants Analyzed 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24
(9 to 45)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Hide Arm/Group Description oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole, (400 mg TID) + oral hydrocortisone (20mg AM, 10mg PM) in men with androgen independent prostate cancer (AIPC).
All-Cause Mortality
Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Affected / at Risk (%) # Events
Total   14/51 (27.45%)    
Gastrointestinal disorders   
Constipation   1/51 (1.96%)  1
Gastric ulcer haemorrhage   1/51 (1.96%)  1
Nausea   1/51 (1.96%)  1
Pancreatitis acute   1/51 (1.96%)  1
Vomiting   1/51 (1.96%)  1
Metabolism and nutrition disorders   
Dehydration   1/51 (1.96%)  1
Hypercalcaemia   3/51 (5.88%)  3
Hypernatraemia   1/51 (1.96%)  1
Hypokalaemia   2/51 (3.92%)  2
Musculoskeletal and connective tissue disorders   
Muscular weakness   2/51 (3.92%)  2
Nervous system disorders   
Cerebrovascular accident   1/51 (1.96%)  1
Cervical cord compression   1/51 (1.96%)  1
Headache   1/51 (1.96%)  1
Hemiparesis   1/51 (1.96%)  1
Spinal cord compression   1/51 (1.96%)  1
Visual field defect   1/51 (1.96%)  1
Renal and urinary disorders   
Renal failure acute   2/51 (3.92%)  2
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism   2/51 (3.92%)  2
Respiratory failure   2/51 (3.92%)  2
Vascular disorders   
Hypertension   1/51 (1.96%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I/II: Oral Calcitriol, Ketoconazole, Hydrocortisone
Affected / at Risk (%) # Events
Total   50/51 (98.04%)    
Blood and lymphatic system disorders   
Anaemia   8/51 (15.69%)  8
Leukopenia   1/51 (1.96%)  1
Thrombocytopenia   1/51 (1.96%)  1
Cardiac disorders   
Bradycardia   1/51 (1.96%)  1
Sinus bradycardia   1/51 (1.96%)  1
Tachycardia   1/51 (1.96%)  1
Eye disorders   
Glaucoma   1/51 (1.96%)  1
Lacrimation increased   1/51 (1.96%)  1
Gastrointestinal disorders   
Abdominal pain   2/51 (3.92%)  2
Constipation   6/51 (11.76%)  6
Diarrhoea   3/51 (5.88%)  3
Dry mouth   2/51 (3.92%)  2
Dyspepsia   7/51 (13.73%)  7
Dysphagia   3/51 (5.88%)  3
Gastrooesophageal reflux disease   1/51 (1.96%)  1
Lip dry   1/51 (1.96%)  1
Nausea   28/51 (54.90%)  28
Vomiting   18/51 (35.29%)  18
General disorders   
Asthenia   3/51 (5.88%)  3
Chest discomfort   1/51 (1.96%)  1
Fatigue   24/51 (47.06%)  24
Gait disturbance   2/51 (3.92%)  2
Influenza like illness   1/51 (1.96%)  1
Malaise   1/51 (1.96%)  1
Oedema peripheral   2/51 (3.92%)  2
Pain   3/51 (5.88%)  3
Hepatobiliary disorders   
Hyperbilirubinaemia   1/51 (1.96%)  1
Immune system disorders   
Hypersensitivity   1/51 (1.96%)  1
Infections and infestations   
Cystitis   1/51 (1.96%)  1
Ear infection   1/51 (1.96%)  1
Herpes zoster   1/51 (1.96%)  1
Nasopharyngitis   2/51 (3.92%)  2
Pneumonia   2/51 (3.92%)  2
Sinusitis   1/51 (1.96%)  1
Upper respiratory tract infection   3/51 (5.88%)  3
Urinary tract infection   3/51 (5.88%)  3
Injury, poisoning and procedural complications   
Arthropod bite   1/51 (1.96%)  1
Fall   1/51 (1.96%)  1
Investigations   
Alanine aminotransferase increased   4/51 (7.84%)  4
Aspartate aminotransferase increased   7/51 (13.73%)  7
Blood alkaline phosphatase increased   3/51 (5.88%)  3
Blood bilirubin increased   1/51 (1.96%)  1
Blood calcium abnormal   1/51 (1.96%)  1
Blood calcium increased   1/51 (1.96%)  1
Blood creatine increased   1/51 (1.96%)  1
Blood creatinine increased   23/51 (45.10%)  23
Blood phosphorus   1/51 (1.96%)  1
Blood phosphorus increased   1/51 (1.96%)  1
Blood potassium decreased   1/51 (1.96%)  1
Blood potassium increased   1/51 (1.96%)  1
Carbon dioxide abnormal   1/51 (1.96%)  1
Glomerular filtration rate decreased   1/51 (1.96%)  1
Glycosylated haemoglobin increased   1/51 (1.96%)  1
Haematocrit decreased   1/51 (1.96%)  1
Haemoglobin decreased   2/51 (3.92%)  2
International normalised ratio increased   1/51 (1.96%)  1
Low density lipoprotein increased   1/51 (1.96%)  1
Prothrombin time prolonged   1/51 (1.96%)  1
Red blood cell count decreased   1/51 (1.96%)  1
Weight decreased   2/51 (3.92%)  2
White blood cell count decreased   1/51 (1.96%)  1
Metabolism and nutrition disorders   
Decreased appetite   10/51 (19.61%)  10
Dehydration   4/51 (7.84%)  4
Hypercalcaemia   28/51 (54.90%)  28
Hyperglycaemia   8/51 (15.69%)  8
Hyperkalaemia   3/51 (5.88%)  3
Hypernatraemia   4/51 (7.84%)  4
Hyperphosphataemia   1/51 (1.96%)  1
Hypoglycaemia   1/51 (1.96%)  1
Hypokalaemia   5/51 (9.80%)  5
Hypophosphataemia   1/51 (1.96%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia   3/51 (5.88%)  3
Back pain   2/51 (3.92%)  2
Flank pain   2/51 (3.92%)  2
Muscle spasms   1/51 (1.96%)  1
Muscular weakness   4/51 (7.84%)  4
Musculoskeletal pain   1/51 (1.96%)  1
Neck pain   2/51 (3.92%)  2
Pain in extremity   3/51 (5.88%)  3
Nervous system disorders   
Ataxia   1/51 (1.96%)  1
Cranial nerve disorder   1/51 (1.96%)  1
Dizziness   5/51 (9.80%)  5
Dysarthria   1/51 (1.96%)  1
Dysgeusia   1/51 (1.96%)  1
Headache   5/51 (9.80%)  5
Neuropathy peripheral   1/51 (1.96%)  1
Somnolence neonatal   1/51 (1.96%)  1
Psychiatric disorders   
Anxiety   1/51 (1.96%)  1
Confusional state   3/51 (5.88%)  3
Renal and urinary disorders   
Dysuria   1/51 (1.96%)  1
Haematuria   3/51 (5.88%)  3
Nephrolithiasis   1/51 (1.96%)  1
Nocturia   1/51 (1.96%)  1
Renal failure acute   1/51 (1.96%)  1
Urinary retention   1/51 (1.96%)  1
Reproductive system and breast disorders   
Pelvic pain   1/51 (1.96%)  1
Respiratory, thoracic and mediastinal disorders   
Cough   1/51 (1.96%)  1
Dyspnoea   3/51 (5.88%)  3
Pneumonitis   1/51 (1.96%)  1
Rhinorrhoea   1/51 (1.96%)  1
Upper-airway cough syndrome   1/51 (1.96%)  1
Skin and subcutaneous tissue disorders   
Dry skin   7/51 (13.73%)  7
Hyperhidrosis   2/51 (3.92%)  2
Nail discolouration   1/51 (1.96%)  1
Nail disorder   1/51 (1.96%)  1
Onychoclasis   1/51 (1.96%)  1
Petechiae   1/51 (1.96%)  1
Pruritus   1/51 (1.96%)  1
Rash   4/51 (7.84%)  4
Surgical and medical procedures   
Cataract operation   1/51 (1.96%)  1
Vascular disorders   
Hot flush   2/51 (3.92%)  2
Hypertension   3/51 (5.88%)  3
Hypotension   1/51 (1.96%)  1
Varicose vein   1/51 (1.96%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Senior Administrator, Compliance - Clinical Research Services
Organization: Roswell Park Cancer Institute
Phone: 716-845-2300
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00536991     History of Changes
Other Study ID Numbers: I 68905
NCI-2011-00129 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RPCI-I-68905
I 68905 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Submitted: September 27, 2007
First Posted: September 28, 2007
Results First Submitted: April 5, 2017
Results First Posted: May 15, 2017
Last Update Posted: June 14, 2017