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

Phase II Study of Weekly Intravenous 1,25 Dihydroxycholecelciferol (Calcitriol) + Dexamethasone in Androgen Independent Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: dexamethasone; Dietary supplement: calcitriol; Genetic: protein expression analysis

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.	Other: laboratory biomarker analysis; Correlative Study; Drug: dexamethasone; Oral; Dietary supplement: calcitriol; IV; Genetic: protein expression analysis; Correlative Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (Complete or Partial Response)	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.	1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: August 31, 2007
• First Submitted That Met QC Criteria: August 31, 2007
• First Posted (Estimate): September 3, 2007

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: recurrent prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Dexamethasone; Calcitriol
• Other Study ID Numbers: CDR0000563197; RPCI I-65405 (Other Identifier: Roswell Park Cancer Institute)