NCT00002760

Brief Summary

RATIONALE: Antiandrogen withdrawal may be an effective treatment for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of ketoconazole and hydrocortisone for antiandrogen withdrawal in treating men with prostate cancer that is refractory to hormone therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
260

participants targeted

Target at P25-P50 for phase_3 prostate-cancer

Timeline
Completed

Started Aug 1996

Longer than P75 for phase_3 prostate-cancer

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 1996

Completed
3.3 years until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2004

Completed
5 months until next milestone

First Posted

Study publicly available on registry

July 19, 2004

Completed
4.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
Last Updated

June 28, 2016

Status Verified

June 1, 2016

Enrollment Period

7.6 years

First QC Date

November 1, 1999

Last Update Submit

June 27, 2016

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostaterecurrent prostate cancer

Outcome Measures

Primary Outcomes (1)

  • Response: PSA

    q 8 wks, at cross over (if applicable), at progression; q 6 mon in f/u

Secondary Outcomes (2)

  • Circulating prostate cancer cells

    Pre treatment, 1 time

  • Adrenal androgen synthesis suppression

    pre tx, after 1 and 3 months tx, at progression

Study Arms (2)

Antiandrogen withdrawal

OTHER

antiandrogen therapy withdrawn; patient who progress will be "crossed over" to Arm 1A: 400 mg ketoconazole PO tid and hydrocortisone 30 mgs PO q am and 10 mgs PO qhs until treatment is no longer effective

Other: Withdrawal of antiandrogen therapy

Antiandrogen withdrawal + therapy

ACTIVE COMPARATOR

Ketoconazole and hydrocortisone

Drug: ketoconazoleDrug: therapeutic hydrocortisone

Interventions

ketoconazoleDRUG

400 mg PO tid for as long as treatment is effective

Antiandrogen withdrawal + therapy
therapeutic hydrocortisoneDRUG

hydrocortisone 30 mg PO q am and 10 mg PO qhs for as long as treatment is effective

Antiandrogen withdrawal + therapy
Withdrawal of antiandrogen therapyOTHER

no drugs given

Antiandrogen withdrawal

Eligibility Criteria

AgeUp to 120 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: Histologically diagnosed adenocarcinoma of the prostate Progressive metastatic or regional nodal disease after at least 4 weeks on flutamide, bicalutamide, or nilutamide, i.e.: Greater than 25% increase in sum of products of perpendicular diameters of all measurable lesions not previously irradiated OR Prostate-specific antigen (PSA) at least 5 ng/mL and risen from baseline on at least 2 successive occasions at least 2 weeks apart PSA progression required for "bone only" disease or disease that responded to androgen deprivation and is negative on imaging scans at entry Primary testicular androgen suppression with a luteinizing hormone-releasing hormone (LHRH) analogue plus antiandrogen or by orchiectomy required Intermittent LHRH analog/antiandrogen therapy resumed at least 4 weeks prior to and continued at time of entry LHRH analogue continued throughout study in absence of orchiectomy PATIENT CHARACTERISTICS: Age: Any age Performance status: 0-2 Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 times normal AST no greater than 3 times normal Renal: Not specified Other: No active, uncontrolled condition including: Bacterial, viral, or fungal infection Hyperglycemia Gastric or duodenal ulcer No existing medical condition requiring systemic corticosteroids (inhaled and topical steroids allowed) No concurrent use of the following: Terfenadine Astemizole Cisapride PRIOR CONCURRENT THERAPY: No prior therapy with experimental agents for metastatic disease Biologic therapy: No prior immunotherapy for metastatic disease Chemotherapy: No prior estramustine or other chemotherapy for metastatic disease Endocrine therapy: See Disease Characteristics No prior hormonal therapy for metastatic disease No prior aminoglutethimide No prior ketoconazole No prior hydrocortisone or other corticosteroids Prior experimental hormonal therapy requires approval of study chair Radiotherapy: At least 4 weeks since radiotherapy (8 weeks since strontium therapy) Surgery: Orchiectomy allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (2)

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (9)

  • D'Amico AV, Halabi S, Vogelzang NJ, et al.: A reduction in the rate of PSA rise following chemotherapy in patients with metastatic hormone refractory prostate cancer (HRPC) predicts survival: results of a pooled analysis of CALGB HRPC trials. [Abstract] J Clin Oncol 22 (Suppl 14): A-4506, 383s, 2004.

    BACKGROUND

  • Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003 Apr 1;21(7):1232-7. doi: 10.1200/JCO.2003.06.100.

    PMID: 12663709BACKGROUND

  • Gilligan TD, Halabi S, Kantoff PW, et al.: African-American race is associated with longer survival in patients with metastatic hormone-refractory prostate cancer (HRCaP) in four randomized phase III Cancer and Leukemia Group B (CALGB) trials. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-725, 2002.

    BACKGROUND

  • Ryan CJ, Halabi S, Ou SS, Vogelzang NJ, Kantoff P, Small EJ. Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study. Clin Cancer Res. 2007 Apr 1;13(7):2030-7. doi: 10.1158/1078-0432.CCR-06-2344.

    PMID: 17404083RESULT

  • Ryan CJ, Halabi S, Kaplan E, et al.: Use of adrenal androgen levels to predict response to ketoconazole in patients with androgen independent prostate cancer: results from CALGB 9583. [Abstract] J Clin Oncol 22 (Suppl 14): A-4558, 396s, 2004.

    RESULT

  • Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. doi: 10.1200/JCO.2004.06.037.

    PMID: 15020604RESULT

  • Halabi S, Small EJ, Hayes DF, Vogelzang NJ, Kantoff PW. Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583. J Clin Oncol. 2003 Feb 1;21(3):490-5. doi: 10.1200/JCO.2003.04.104.

    PMID: 12560440RESULT

  • Halabi S, Small E, Farmer D, et al.: Reverse transcriptase polymerase chain reaction (RT-PCR) for prostate specific antigen (PSA) as a prognostic factor for survival among androgen independent prostate cancer patients (AICaP): a companion study to CALGB 9583. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-700, 2001.

    RESULT

  • Vogelzang NV, Halabi S, Picus J, et al.: Prospective assessment of adrenal androgen levels as predictors of survival in androgen independent prostate cancer patients treated with ketoconazole: a correlative study to CALGB protocol 9583. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-749, 2001.

    RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

KetoconazoleHydrocortisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

PiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-Hydroxycorticosteroids

Study Officials

  • Eric Small, MD

    University of California, San Francisco

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 1999

First Posted

July 19, 2004

Study Start

August 1, 1996

Primary Completion

March 1, 2004

Study Completion

April 1, 2009

Last Updated

June 28, 2016

Record last verified: 2016-06

Locations

US(2)