Official Title: “Phase I Study Of Oral, 1,25 Dihydroxycholecalciferol (Calcitriol) + Dexamethasone In Hormone-Refractory Prostate Cancer”

RATIONALE: Combining calcitriol with dexamethasone may increase the effectiveness of therapy by making cancer cells more sensitive to dexamethasone.

PURPOSE: Phase I trial to study the effectiveness of calcitriol combined with dexamethasone in treating patients who have prostate cancer that has not responded to previous hormone therapy.

Study Type: Interventional

Study Design: Treatment

OBJECTIVES: - Determine the maximum tolerated dose of calcitriol administered alone and in combination with dexamethasone in patients with hormone-refractory prostate cancer. - Determine the pharmacokinetics of calcitriol with and without dexamethasone in these patients.

OUTLINE: This is a dose-escalation study of calcitriol.

In the first stage of the study, cohorts of 3-6 patients receive escalating doses of oral calcitriol on days 1-3. Dose escalation continues until the maximum tolerated dose (MTD) is determined.

In the second stage, patients receive escalating doses of oral calcitriol on days 1-3 and a fixed dose of oral dexamethasone on days 0-4. Treatment continues weekly in the absence of disease progression or unacceptable toxicity. Dose escalation continues until the MTD is determined.

Six additional patients may receive calcitriol and dexamethasone at one dose level below the MTD determined in the second stage, to confirm the MTD.

The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: calcitriol
• Drug: dexamethasone

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate with progressing regional or metastatic disease despite primary hormonal therapy (bilateral orchiectomy, estrogen, or luteinizing hormone-releasing hormone (LHRH) therapy with or without simultaneous antiandrogen)
• Documented new lesions or rising PSA (at least 50% increase on 3 measurements more than 2 weeks apart) after prior antiandrogen or progestational agent, or other hormonal agent cessation

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,500/mm^3
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGOT less than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.8 mg/dL

Other:

• No uncontrolled diabetes mellitus
• Fertile patients must use effective double barrier contraception for at least 1 week before, during, and at least 2 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Concurrent epoetin alfa for anemia allowed

Chemotherapy:

• Not specified

Endocrine therapy:

• See Disease Characteristics
• At least 28 days since prior antiandrogens or progestational agents
• Concurrent testicular androgen suppression with an LHRH analog (leuprolide or goserelin) allowed in non-orchidectomized patients

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No concurrent bisphosphonates

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: UPMC Cancer Centers

Overall Clinical Trial Officials and Contacts

Gurkamal S. Chatta, MD Study Chair UPMC Cancer Centers  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00010231

Study ID Number: CDR0000068457

ClinicalTrials.gov Identifier: NCT00010231

Health Authority: United States: Federal Government

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