A Phase II Trial of Early Medical Adrenalectomy for "D0.5" Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00006371
• Recruitment Status: Terminated
• First Posted: April 2, 2004
• Last Update Posted: September 27, 2012
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Cancer Institute (NCI); Janssen Pharmaceuticals
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: October 4, 2000
• First Posted Date: April 2, 2004
• Last Update Posted Date: September 27, 2012
• Study Start Date: May 2000
• Actual Primary Completion Date: December 2001 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 25, 2012)

Objective Response Rate (ORR) for Treatment Arm [ Time Frame: 1 year ]

Determine the PSA response proportion and duration of response of patients with localized stage IV (D0.5) adenocarcinoma of the prostate treated with early medical adrenalectomy using hydrocortisone combined with aminoglutethimide or ketoconazole after prior antiandrogen withdrawal.

• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00006371 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II Trial of Early Medical Adrenalectomy for "D0.5" Prostate Cancer
• Official Title: A Phase II Trial of Early Medical Adrenalectomy for "D0.5" Prostate Cancer

Brief Summary

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as aminoglutethimide or ketoconazole may stop the adrenal glands from producing hormones. Combining hydrocortisone with either aminoglutethimide or ketoconazole may be an effective treatment for prostate cancer.

PURPOSE: Phase II trial to study the effectiveness of combining hydrocortisone with either aminoglutethimide or ketoconazole in treating patients who have localized stage IV prostate cancer.

Detailed Description

OBJECTIVES: I. Determine the Prostate-Specific Antigen (PSA) response proportion and duration of response of patients with localized stage IV (D0.5) adenocarcinoma of the prostate treated with early medical adrenalectomy using hydrocortisone combined with aminoglutethimide or ketoconazole after prior antiandrogen withdrawal. II. Compare the incidence of grades 3-4 toxicities of these regimens in these patients. III. Correlate adrenal androgen suppression with response in these patients.

OUTLINE: Patients are stratified according to prior antiandrogen therapy (yes vs no). Patients with prior antiandrogen therapy begin study therapy after appropriate antiandrogen withdrawal, while those without such prior therapy begin study therapy immediately. Patients undergo medical adrenalectomy using hydrocortisone combined with aminoglutethimide OR ketoconazole. Oral hydrocortisone is administered twice daily. Oral aminoglutethimide is administered twice daily for 1 week and then 4 times daily during subsequent weeks. Oral ketoconazole is administered three times daily. Combination treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: aminoglutethimide
  Other Name: Cytadren
• Drug: ketoconazole
  Other Name: Nizoral
• Drug: therapeutic hydrocortisone
  Other Name: corticosteroid

Study Arms

• Active Comparator: Hydrocortisone with Ketoconazole
  Patients are stratified according to prior antiandrogen therapy (yes vs no). Patients with prior antiandrogen therapy begin study therapy after appropriate antiandrogen withdrawal, while those without such prior therapy begin study therapy immediately. Patients undergo medical adrenalectomy using hydrocortisone combined with ketoconazole. Oral hydrocortisone is administered twice daily. Oral aminoglutethimide is administered twice daily for 1 week and then 4 times daily during subsequent weeks. Oral ketoconazole is administered three times daily.
  Interventions:

  • Drug: ketoconazole
  • Drug: therapeutic hydrocortisone
• Active Comparator: Hydrocortisone with Aminoglutethimide
  Patients are stratified according to prior antiandrogen therapy (yes vs no). Patients with prior antiandrogen therapy begin study therapy after appropriate antiandrogen withdrawal, while those without such prior therapy begin study therapy immediately. Patients undergo medical adrenalectomy using hydrocortisone combined with aminoglutethimide. Oral hydrocortisone is administered twice daily. Oral aminoglutethimide is administered twice daily for 1 week and then 4 times daily during subsequent weeks. Oral ketoconazole is administered three times daily.
  Interventions:

  • Drug: aminoglutethimide
  • Drug: therapeutic hydrocortisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 25, 2012): 2
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2001
• Actual Primary Completion Date: December 2001 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the prostate Stage IV (D0.5; no evidence of disease on CT or bone scan after testicular androgen ablation) PSA progression after testicular androgen ablation with or without antiandrogen therapy Progression is defined as at least 2 consecutive rising PSA levels (drawn at least 2 weeks apart) with a greater than 50% rise above the last nadir level (arbitrary PSA at least 2 ng/dL)

PATIENT CHARACTERISTICS: Age: Not specified Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No other medical conditions that would increase risk Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: See Disease Characteristics Greater than 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide) No prior aminoglutethimide or ketoconazole for prostate cancer Continuation of primary testicular androgen suppression (i.e., LHRH analog) required Radiotherapy: Not specified Surgery: Not specified Other: No concurrent terfenadine, astemizole, cisapride, or other medicines known to interact with ketoconazole

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00006371
• Other Study ID Numbers: MCC-12219; NCI-G00-1863 ( Other Identifier: NCI )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Collaborators

• National Cancer Institute (NCI)
• Janssen Pharmaceuticals

Investigators

• Principal Investigator: Mayer Fishman, M.D., Ph.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: September 2012