Calcitriol Plus Dexamethasone in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy

Sponsor

University of Pittsburgh (Other)

Overall Status

Completed

CT.gov ID

NCT00010231

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Dietary Supplement: calcitriol Drug: dexamethasone	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study Of Oral, 1,25 Dihydroxycholecalciferol (Calcitriol) + Dexamethasone In Hormone-refractory Prostate Cancer

Study Start Date :

Jun 1, 1999

Actual Primary Completion Date :

Aug 1, 2002

Actual Study Completion Date :

Nov 1, 2002

Outcome Measures

Primary Outcome Measures

MTD of calcitriol (oral) administered for 3 days (Monday, Tuesday, Wednesday -MTW) weekly in men with hormone-refractory prostate cancer [1 year]
MTD of calcitriol (oral, MTW weekly + dexamethasone (oral, Sunday, Monday, Tuesday, Wednesday - SMTW) in men with hormone refractory prostate cancer [1 year]

Secondary Outcome Measures

whether dexamethasone permits the administration of calcitriol without the development of hypercalcemia in patients who developed hypercalcemia while receiving calcitriol alone [1 year]
pharmacokinetics of calcitriol when given as a single agent and following 3 days of dexamethasone [1 year]
effects of calcitriol +/- dexamethasone on serum PTH, urinary calcium and MAPK activity and VDR expression in serum, urine and PBMs , respectively, in this patient population [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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