Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer

NCT00003653 | Completed Phase 3 DMC

• 5 other identifiers: PR7CAN-NCIC-PR7SWOG-JPR7ICR-CTSU-JPR7CDR0000066745
• Study Type: interventional
• Target: 1,386
• Locations: 1 country
• Sites: 29

Brief Summary

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. It is not yet known which androgen suppression regimen is more effective for prostate cancer. PURPOSE: This randomized phase III trial is studying two hormone therapy regimens and comparing them to see how well they work in treating patients with rising PSA levels following radiation therapy for prostate cancer.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; recurrent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

  2 years

Secondary Outcomes (6)

• Time to hormone resistance

  2 years

• Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist

  2 years

• Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels

  2 years

• Duration of treatment and non-treatment interval during intermittent androgen suppression arm only

  2 years

• Time to testosterone recovery during intermittent androgen suppression arm only

  2 years

Study Arms (2)

Intermittent Androgen Suppression

ACTIVE COMPARATOR

Drug: bicalutamide; Drug: buserelin; Drug: cyproterone acetate; Drug: flutamide; Drug: goserelin; Drug: leuprolide acetate; Drug: nilutamide

Continuous Androgen Suppression

ACTIVE COMPARATOR

Drug: bicalutamide; Drug: buserelin; Drug: cyproterone acetate; Drug: flutamide; Drug: goserelin; Drug: leuprolide acetate; Drug: nilutamide

Interventions

bicalutamide DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

buserelin DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

cyproterone acetate DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

flutamide DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

goserelin DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

leuprolide acetate DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

nilutamide DRUG

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Continuous Androgen Suppression; Intermittent Androgen Suppression

Eligibility Criteria

• Age: 16 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically proven adenocarcinoma of the prostate prior to the initiation of radiotherapy * Prior pelvic radiotherapy for prostate cancer, either post-radical prostatectomy or as primary management * More than 30 months since prior brachytherapy with curative intent * Prostate-specific antigen must be rising and greater than 3 ng/mL and higher than the lowest level recorded previously since the end of radiotherapy (i.e., higher than the post-radiotherapy nadir) * Total testosterone greater than 5 nmol/L * No definite evidence of metastatic disease * Chest x-ray and bone scan negative for metastases * Radiological changes compatible with nonmalignant diseases allowed * Clinical evidence of local disease allowed PATIENT CHARACTERISTICS: Age: * 16 and over (18 and over for participating centers in the United Kingdom) Performance status: * ECOG 0-1 Life expectancy: * More than 5 years Hematopoietic: * Not specified Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * AST/ALT no greater than 1.5 times ULN * LDH no greater than 1.5 times ULN * No chronic liver disease Renal: * Creatinine no greater than 1.5 times ULN Other: * Sufficiently fluent and willing to complete the quality of life questionnaire in either English or French * Fertile patients must use effective contraception * No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or superficial bladder cancer PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior or concurrent biologic therapy Chemotherapy: * No prior or concurrent chemotherapy Endocrine therapy: * Prior hormonal therapy administered prior to, during, or immediately after radical radiotherapy or prostatectomy allowed provided duration was no longer than 12 months * At least 12 months since prior hormonal therapy Radiotherapy: * See Disease Characteristics * At least 12 months since prior radiotherapy * No concurrent palliative radiotherapy Surgery: * See Disease Characteristics * See Endocrine therapy Other: * No concurrent bisphosphonates

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

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• National Cancer Institute (NCI): collaborator
• SWOG Cancer Research Network: collaborator

Study Sites (29)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

Clinical Research Unit at Vancouver Coastal

Vancouver, British Columbia, V5Z 1M9, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

William Osler Health Centre, Brampton Memorial

Brampton, Ontario, L6R 3J7, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (4)

• Klotz L, Correia A, Zhang W. The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer. Prostate Cancer Prostatic Dis. 2005;8(2):179-83. doi: 10.1038/sj.pcan.4500792.

  PMID: 15809670 BACKGROUND

• Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. doi: 10.1056/NEJMoa1201546.

  PMID: 22931259 RESULT

• Hamilton RJ, Ding K, Crook JM, O'Callaghan CJ, Higano CS, Dearnaley DP, Horwitz EM, Goldenberg SL, Gospodarowicz MK, Klotz L. The Association Between Statin Use and Outcomes in Patients Initiating Androgen Deprivation Therapy. Eur Urol. 2021 Apr;79(4):446-452. doi: 10.1016/j.eururo.2020.12.031. Epub 2020 Dec 31.

  PMID: 33390282 DERIVED

• Klotz L, O'Callaghan C, Ding K, Toren P, Dearnaley D, Higano CS, Horwitz E, Malone S, Goldenberg L, Gospodarowicz M, Crook JM. Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT. J Clin Oncol. 2015 Apr 1;33(10):1151-6. doi: 10.1200/JCO.2014.58.2973. Epub 2015 Mar 2.

  PMID: 25732157 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Buserelin; Cyproterone Acetate; Flutamide; Goserelin; Leuprolide; nilutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Cyproterone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Laurence H. Klotz, MD

  Toronto Sunnybrook Regional Cancer Centre

  STUDY CHAIR

• Celestia S. Higano, MD

  University of Washington

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: January 5, 1999
• Primary Completion: October 4, 2010
• Study Completion: January 10, 2013
• Last Updated: June 23, 2021

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (29)