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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00010231
• Other study ID #: PCI-99044
• Secondary ID: CDR0000068457PCI
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2001
• Last updated: March 27, 2015
• Start date: June 1999
• Est. completion date: November 2002

Study information

• Verified date: March 2015
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 2002
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Dietary Supplement:
• calcitriol

Drug:
• dexamethasone

Locations

Country	Name	City	State
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of calcitriol (oral) administered for 3 days (Monday, Tuesday, Wednesday -MTW) weekly in men with hormone-refractory prostate cancer		1 year	No
Primary	MTD of calcitriol (oral, MTW weekly + dexamethasone (oral, Sunday, Monday, Tuesday, Wednesday - SMTW) in men with hormone refractory prostate cancer		1 year	No
Secondary	whether dexamethasone permits the administration of calcitriol without the development of hypercalcemia in patients who developed hypercalcemia while receiving calcitriol alone		1 year	No
Secondary	pharmacokinetics of calcitriol when given as a single agent and following 3 days of dexamethasone		1 year	No
Secondary	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	No