Calcitriol, Mitoxantrone, and Prednisone in Treating Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Calcitriol may cause prostate cancer cells to look more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as mitoxantrone and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well giving calcitriol together with mitoxantrone and prednisone works in treating patients with metastatic prostate cancer.

Detailed Description
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OBJECTIVES: Primary Determine the prostate-specific antigen (PSA) response rate, defined as the fraction of patients with 50% reduction in PSA level over 3 weeks' time, in patients with androgen-independent metastatic prostate cancer treated with high-dose pulse calcitriol, mitoxantrone, and prednisone. Secondary Determine the safety and tolerability of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral high dose pulse calcitriol on day 1, mitoxantrone IV on day 2, and oral prednisone on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

Official Title
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Phase II Study of DN-101 (High Dose Pulse Calcitriol), Mitoxantrone, Prednisone in Androgen-Independent Prostate Cancer (AIPC)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Drug: mitoxantrone hydrochloride
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed prostate cancer Androgen-independent disease, defined as disease progression while on standard hormonal management, including antiandrogen withdrawal Patients must continue primary hormonal therapy during study treatment Regional or distant metastases Prostate-specific antigen > 5 ng/mL No brain metastases PATIENT CHARACTERISTICS: Age 18 to 100 Performance status ECOG 0-3 Life expectancy Not specified Hematopoietic Adequate hematologic function Hepatic Adequate hepatic function Renal Adequate renal function No calcium-salt kidney stones within the past 5 years No hypercalcemia Cardiovascular Adequate cardiac function No significant cardiac disease No atrial fibrillation Other Fertile patients must use effective barrier contraception during and for 2 months after completion of study treatment No other serious medical illness No other active malignancy except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy More than 28 days since prior biologic therapy Chemotherapy No prior chemotherapy Endocrine therapy See Disease Characteristics Radiotherapy No prior strontium chloride Sr 89 More than 28 days since prior radiotherapy More than 56 days since prior samarium Sm 153 lexidronam pentasodium Surgery Prior prostatectomy and/or orchiectomy allowed Other More than 28 days since prior investigational therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: calcitriol|nan|
|Drug: mitoxantrone hydrochloride|nan|
|Drug: prednisone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in serum prostate-specific antigen (PSA) by 50% measured every 21 days |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by Common Toxicity Criteria v3.0 |  |  | 
| Frozen plasma and serum samples for correlative biomarker analysis collected every 21 days |  |  | 
| Confirmed PSA reduction > 75% measured every 21 days |  |  | 
| PSA normalization (< 4 ng/mL) measured every 21 days |  |  | 
| Response to measurable disease as measured by RECIST criteria every 9 weeks |  |  | 
| Analgesic response as measured by McGill-Melzack Pain Questionnaire every 21 days |  |  | 
| Analgesic medication use decreased by ≥ 50% without an increase in pain for 2 consecutive evaluations at least 3 weeks apart |  |  | 
| Palliative response as measured by McGill-Melzack Pain Questionnaire every 21 days |  |  | 
| Quality of life as measured by EORTC core questionnaire Quality of Life-C30 every 21 days |  |  | 
| Time to palliative-progression as measured by McGill-Melzack Pain Questionnaire every 21 days |  |  | 
| Time to PSA progression measured every 21 days |  |  | 
| Time to progression in measurable or evaluable disease as measured by whole body scan and/or CT or MRI scan every 9-12 weeks |  |  | 
| Time to death assessed every 6 months after completion of study treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent prostate cancer, stage IV prostate cancer