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

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: calcitriol
• Drug: mitoxantrone hydrochloride
• Drug: prednisone

Primary Measures

• Reduction in serum prostate-specific antigen (PSA) by 50% measured every 21 days
  • Safety Issue?: No

Secondary Measures

• Toxicity as measured by Common Toxicity Criteria v3.0
  • Safety Issue?: Yes
• Frozen plasma and serum samples for correlative biomarker analysis collected every 21 days
  • Safety Issue?: No
• Confirmed PSA reduction > 75% measured every 21 days
  • Safety Issue?: No
• PSA normalization (< 4 ng/mL) measured every 21 days
  • Safety Issue?: No
• Response to measurable disease as measured by RECIST criteria every 9 weeks
  • Safety Issue?: No
• Analgesic response as measured by McGill-Melzack Pain Questionnaire every 21 days
  • Safety Issue?: No
• Analgesic medication use decreased by ≥ 50% without an increase in pain for 2 consecutive evaluations at least 3 weeks apart
  • Safety Issue?: No
• Palliative response as measured by McGill-Melzack Pain Questionnaire every 21 days
  • Safety Issue?: No
• Quality of life as measured by EORTC core questionnaire Quality of Life-C30 every 21 days
  • Safety Issue?: No
• Time to palliative-progression as measured by McGill-Melzack Pain Questionnaire every 21 days
  • Safety Issue?: No
• Time to PSA progression measured every 21 days
  • Safety Issue?: No
• Time to progression in measurable or evaluable disease as measured by whole body scan and/or CT or MRI scan every 9-12 weeks
  • Safety Issue?: No
• Time to death assessed every 6 months after completion of study treatment
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Oregon Health and Science University Cancer Institute

Overall Clinical Trial Officials and Contacts

Christopher W. Ryan, MD Study Chair Oregon Health and Science University Cancer Institute  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00182741

Study ID Number: CDR0000441172

ClinicalTrials.gov Identifier: NCT00182741

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database