Clinical trial NCT00010231: Calcitriol Plus Dexamethasone in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy
Official title: Phase I Study Of Oral, 1,25 Dihydroxycholecalciferol (Calcitriol) + Dexamethasone In Hormone-refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-06
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: MTD of calcitriol (oral) administered for 3 days (Monday, Tuesday, Wednesday -MTW) weekly in men with hormone-refractory prostate cancer
timeFrame: 1 year
measure: MTD of calcitriol (oral, MTW weekly + dexamethasone (oral, Sunday, Monday, Tuesday, Wednesday - SMTW) in men with hormone refractory prostate cancer
timeFrame: 1 year
Secondary outcomes:
measure: whether dexamethasone permits the administration of calcitriol without the development of hypercalcemia in patients who developed hypercalcemia while receiving calcitriol alone
timeFrame: 1 year
measure: pharmacokinetics of calcitriol when given as a single agent and following 3 days of dexamethasone
timeFrame: 1 year
measure: 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
timeFrame: 1 year
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Gurkamal S. Chatta, MD
role: STUDY_CHAIR
References: