A Phase II Trial of Calcitriol and Naproxen in Patients With Recurrent Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
To determine whether, in this patient population, treatment with calcitriol and Naproxen is more effective in delaying the growth of prostate cancer than treatment with calcitriol alone as seen in historical controls.

Detailed Description
-----------------
In summary, in vitro and in vivo studies, as well as early phase clinical trial, have shown a promising role for both calcitriol and NSAIDs in the treatment of prostate cancer. Moreover, calcitriol and NSAIDs both exert their antiproliferative effect by decreasing prostaglandin levels, but they do so by different mechanisms. Thus, there is reason to believe that their combined effects on prostaglandins may be synergistic. Preliminary in vitro assays in which calcitriol is given in combination with one of two different NSAIDs (Naprosyn or sulindac) to LNCaP cell lines have indicated such synergy. This observation provides the rational for using them in combination for the treatment of prostate cancer. In addition, it is hoped that any synergy noted would allow for the use of lower doses of NSAIDs.

Official Title
-----------------
A Phase II Trial of Calcitriol and Naproxen in Patients With Recurrent Prostate Cancer

Conditions
-----------------
Prostatic Neoplasms, Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Calcitriol
* Drug: Naproxen-n-butyl nitrate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must give written informed consent Histologically confirmed adenocarcinoma of the prostate Biochemical relapse after primary radiation therapy or surgery Normal testosterone levels 3 rising PSA after nadir, with interval between PSA determinations > 2 weeks Exclusion Criteria: Local recurrence by CT scan Distant metastases by bone scan Hypercalcemia Nephrolithiasis Renal insufficiency (serum creatinine > 1.8 mg/dl) Pancreatitis History of ulcer or gastrointestinal bleeding More than 6 months of hormone ablation therapy Concurrent therapy for prostate cancer Uncontrolled HTN H/O MI, CVA, TIA Known coronary disease/cerebrovascular disease Platelet counts <50 Patients on anticoagulants Patients on lithium

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Calcitriol|0.5 micrograms/kilogram q weekly|
|Drug: Naproxen-n-butyl nitrate|400 mg BID, oral|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response - 50% PSA decline, PSA progression, PSA response duration, progressive disease, time to PSA progression. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progressive disease in this study's patients, who would be treated with calcitriol and naprosyn, will be compared to that in historical controls of patients treated with calcitriol alone. |  |  |