Calcitriol and Dexamethasone in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00524589
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 53
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Calcitriol may help prostate cancer cells become more like normal cells, and to grow and spread more slowly. Dexamethasone may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with dexamethasone may be an effective treatment for prostate cancer that did not respond to hormone therapy .

PURPOSE: This phase II trial is studying how well giving calcitriol together with dexamethasone works in treating patients with prostate cancer that did not respond to hormone therapy.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Dietary Supplement: calcitriol; Drug: dexamethasone; Genetic: protein expression analysis; Other: laboratory biomarker analysis	Phase 2

Detailed Description

OBJECTIVES:

• To investigate the response rate in patients with androgen-independent prostate cancer treated with calcitriol and dexamethasone.

• To evaluate the toxicity of high-dose calcitriol and dexamethasone in these patients.

OUTLINE: Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and on days 2 and 3 to assess VDR and CYP24 expression in peripheral blood mononuclear cells.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Weekly Intravenous 1,25 Dihydroxycholecelciferol (Calcitriol) + Dexamethasone in Androgen Independent Prostate Cancer
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexamethasone and Calcitriol Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly.	Dietary Supplement: calcitriol; IV; Drug: dexamethasone; Oral; Genetic: protein expression analysis; Correlative Study; Other: laboratory biomarker analysis; Correlative Study

Outcome Measures

Primary Outcome Measures

1. Objective Response (Complete or Partial Response) [1 year]

   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.

Secondary Outcome Measures

1. Corrected Serum Calcium Expression [1 year]

   Number of patients with corrected serum calcium levels between 11 mg/dL and 12 mg/dL detected on 1 or more occasions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• History of androgen-independent prostate cancer

• Evidence of rising PSA level (with or without new lesion by radiograph or physical examination), defined as follows:

• PSA level > 5 ng/mL and clearly rising on 2 measurements taken ≥ 2 weeks apart after androgen deprivation therapy (i.e., orchiectomy or luteinizing hormone-releasing hormone [LHRH] analogue) and antiandrogen withdrawal, if appropriate

• PSA rising before and on the first value taken at 4 or 6 weeks after antiandrogen cessation is considered disease progression

• Measurable or evaluable disease as defined by any of the following:

• Measurable or evaluable tumor masses by radiograph or physical examination

• Evaluable PSA

• Concurrent LHRH analogue or diethylstilbestrol (DES) for testicular androgen suppression required if no prior bilateral orchiectomy

• Patients receiving other monotherapy for testicular androgen suppression must switch to a LHRH analogue or DES ≥ 14 days prior to study entry

PATIENT CHARACTERISTICS:

• ECOG 0-2

• Life expectancy ≥ 12 weeks

• ANC ≥ 1,000/mm³

• Platelet count ≥ 75,000/mm³

• Hemoglobin > 8.9 g/dL (transfusion or erythropoietin support allowed)

• Serum creatinine ≤ 1.8 mg/dL

• AST ≤ 4 times upper limit of normal (ULN)

• Total bilirubin ≤ 2.0 mg/dL

• Serum corrected calcium < ULN

• No history of nephrolithiasis within the past 5 years

• No unstable, uncontrolled peptic ulcer disease, congestive heart failure, glaucoma, HIV, or diabetes

PRIOR CONCURRENT THERAPY:

• At least 28 days since prior androgen deprivation therapy (≥ 42 days for bicalutamide)

• A 28-day washout period is not required for patients who have previously progressed despite antiandrogen withdrawal and who have resumed antiandrogens without reduction of PSA

• At least 14 days since prior radiotherapy

• At least 28 days since prior strontium 89

• At least 28 days since prior chemotherapy and/or investigational agents

• No concurrent medications or supplements that contain additional calcium (e.g., Tums)

• No concurrent radiotherapy for pain control or any other indication

• Concurrent bisphosphonates allowed provided dose/regimen is stable

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

Investigators

• Principal Investigator: Donald L. Trump, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00524589
• Other Study ID Numbers: CDR0000563197; RPCI I-65405
• First Posted: Sep 3, 2007
• Last Update Posted: Nov 20, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Roswell Park Cancer Institute: recurrent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Calcitriol; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	Dexamethasone and Calcitriol
Arm/Group Description	Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. calcitriol: IV dexamethasone: Oral protein expression analysis: Correlative Study laboratory biomarker analysis: Correlative Study
Period Title: Overall Study
STARTED	18
COMPLETED	0
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Dexamethasone and Calcitriol
Arm/Group Description	Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. calcitriol: IV dexamethasone: Oral protein expression analysis: Correlative Study laboratory biomarker analysis: Correlative Study
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (11.8)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 38.9%
>=65 years	11 61.1%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response (Complete or Partial Response)
Description	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	1 year

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Dexamethasone and Calcitriol
Arm/Group Description	Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. calcitriol: IV dexamethasone: Oral protein expression analysis: Correlative Study laboratory biomarker analysis: Correlative Study
Measure Participants	18
Number [percentage of participants]	0 0%

2. Secondary Outcome

Title	Corrected Serum Calcium Expression
Description	Number of patients with corrected serum calcium levels between 11 mg/dL and 12 mg/dL detected on 1 or more occasions.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Dexamethasone and Calcitriol
Arm/Group Description	Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. calcitriol: IV dexamethasone: Oral protein expression analysis: Correlative Study laboratory biomarker analysis: Correlative Study
Measure Participants	18
Count of Participants [Participants]	6 33.3%

Adverse Events

Arm/Group Title	Dexamethasone and Calcitriol
Arm/Group Description	Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. calcitriol: IV dexamethasone: Oral protein expression analysis: Correlative Study laboratory biomarker analysis: Correlative Study
All Cause Mortality
	Dexamethasone and Calcitriol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dexamethasone and Calcitriol
	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)
Cardiac disorders
Angina pectoris	1/18 (5.6%)	2
Arrhythmia	1/18 (5.6%)	2
Palpitations	1/18 (5.6%)	2
Sinus tachycardia	1/18 (5.6%)	2
General disorders
Chest pain	1/18 (5.6%)	2
Investigations
Heart rate irregular	1/18 (5.6%)	2
Metabolism and nutrition disorders
Hypocalcaemia	2/18 (11.1%)	6
Hypophosphataemia	1/18 (5.6%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/18 (11.1%)	4
Other (Not Including Serious) Adverse Events
	Dexamethasone and Calcitriol
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Anaemia	8/18 (44.4%)	22
Thrombocytopenia	2/18 (11.1%)	4
Eye disorders
Vision blurred	1/18 (5.6%)	2
Visual disturbance	1/18 (5.6%)	2
Gastrointestinal disorders
Abdominal pain upper	1/18 (5.6%)	2
Constipation	3/18 (16.7%)	6
Diarrhoea	3/18 (16.7%)	8
Dyspepsia	2/18 (11.1%)	4
Nausea	2/18 (11.1%)	4
Vomiting	1/18 (5.6%)	2
General disorders
Asthenia	1/18 (5.6%)	2
Chest pain	2/18 (11.1%)	4
Fatigue	7/18 (38.9%)	18
Oedema peripheral	2/18 (11.1%)	4
Pain	1/18 (5.6%)	2
Pyrexia	2/18 (11.1%)	4
Infections and infestations
Infection	1/18 (5.6%)	2
Investigations
Aspartate aminotransferase increased	1/18 (5.6%)	2
Blood albumin decreased	1/18 (5.6%)	2
Blood alkaline phosphatase increased	3/18 (16.7%)	6
Blood bilirubin increased	1/18 (5.6%)	2
Blood creatine increased	1/18 (5.6%)	2
Blood creatinine increased	4/18 (22.2%)	18
Blood urea	1/18 (5.6%)	2
Blood urea increased	3/18 (16.7%)	6
Blood urine present	1/18 (5.6%)	2
Metabolism and nutrition disorders
Anorexia	1/18 (5.6%)	2
Hypercalcaemia	8/18 (44.4%)	44
Hyperglycaemia	8/18 (44.4%)	24
Hypoalbuminaemia	2/18 (11.1%)	4
Hypocalcaemia	2/18 (11.1%)	4
Hypoglycaemia	1/18 (5.6%)	2
Hyponatraemia	1/18 (5.6%)	2
Hypophosphataemia	6/18 (33.3%)	12
Musculoskeletal and connective tissue disorders
Arthralgia	2/18 (11.1%)	4
Back pain	4/18 (22.2%)	10
Groin pain	1/18 (5.6%)	2
Neck pain	1/18 (5.6%)	2
Pain in extremity	1/18 (5.6%)	2
Nervous system disorders
Dizziness	2/18 (11.1%)	4
Headache	1/18 (5.6%)	2
Sinus headache	1/18 (5.6%)	2
Tremor	1/18 (5.6%)	2
Psychiatric disorders
Insomnia	2/18 (11.1%)	4
Renal and urinary disorders
Haematuria	2/18 (11.1%)	6
Micturition urgency	2/18 (11.1%)	6
Urinary hesitation	1/18 (5.6%)	2
Urinary retention	1/18 (5.6%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/18 (5.6%)	2
Dyspnoea	2/18 (11.1%)	4
Nasal congestion	1/18 (5.6%)	2
Skin and subcutaneous tissue disorders
Onychoclasis	1/18 (5.6%)	2
Surgical and medical procedures
Dermabrasion	1/18 (5.6%)	2
Vascular disorders
Flushing	4/18 (22.2%)	9
Hypertension	1/18 (5.6%)	2

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.