Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer

NCT00002633 | Completed Phase 3 DMC

• 9 other identifiers: PR3CAN-NCIC-PR3ECOG-JPR03MRC-PR07SWOG-JPR3EU-99013NCI-T94-0110OISRCTN24991896CDR0000064065
• Study Type: interventional
• Target: 361
• Locations: 1 country
• Sites: 15

Brief Summary

RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether hormone therapy plus surgery is more effective than hormone therapy plus radiation therapy for prostate cancer. PURPOSE: This randomized phase III trial is studying giving hormone therapy alone to see how well it works compared to giving hormone therapy together with bilateral orchiectomy or radiation therapy in treating patients with stage III or stage IV prostate cancer.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

  10 years

Secondary Outcomes (4)

• Disease specific survival

  10 years

• Time to disease progression

  10 years

• Symptomatic local control measured by surgical intervention rate

  10 years

• Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire

  10 years

Study Arms (2)

Total Androgen Blockade

ACTIVE COMPARATOR

Drug: bicalutamide; Drug: buserelin; Drug: flutamide; Drug: goserelin; Drug: leuprolide acetate; Drug: nilutamide; Procedure: orchiectomy

Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

ACTIVE COMPARATOR

Drug: bicalutamide; Drug: buserelin; Drug: flutamide; Drug: goserelin; Drug: leuprolide acetate; Drug: nilutamide; Procedure: orchiectomy; Radiation: radiation therapy

Interventions

bicalutamide DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

buserelin DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

flutamide DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

goserelin DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

leuprolide acetate DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

nilutamide DRUG

Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

orchiectomy PROCEDURE

Optional orchiectomy

Total Androgen Blockade; Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

radiation therapy RADIATION

Radical Radiation Therapy - (65-69 Gy; 35-37 treatments)

Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

Eligibility Criteria

• Age: Up to 79 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically proven locally advanced adenocarcinoma of the prostate, defined as 1 of the following: * T3-4, N0 or NX, M0 * T2, PSA greater than 40 µg/L * T2, PSA greater than 20 µg/L AND Gleason score at least 8 * Diagnosis made within the past 6 months * Gleason score and PSA known * Pelvic lymph nodes must be clinically negative * Lymph nodes no more than 1.5 cm in greatest diameter by CT scan or MRI of the pelvis * Negative needle aspirate required for any lymph node more than 1.5 cm * If a lymph node dissection was performed, it must be histologically negative * No small cell or transitional cell carcinoma by biopsy * No bony metastases by bone scan PATIENT CHARACTERISTICS: Age: * Under 80 Performance status: * ECOG 0-2 Life expectancy: * At least 5 years excluding malignancy Hematopoietic: * Hemoglobin at least 10.0 g/dL * WBC at least 2,000/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin less than 2 times upper limit of normal (ULN) * SGOT and SGPT less than 2 times ULN * Alkaline phosphatase less than 2 times ULN * No history of chronic liver disease Renal: * Creatinine less than 2 times ULN Other: * No contraindication to wide-field pelvic irradiation (e.g., inflammatory bowel disease or severe bladder irritability) * No other malignancy within the past 5 years except nonmelanoma skin cancer * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Not specified Endocrine therapy: * Prior hormonal therapy within the past 12 weeks allowed provided the following conditions are met: * Negative bone scan before beginning any hormonal therapy * Extracapsular extension remains palpable on rectal re-exam * Baseline PSA known before beginning any hormonal therapy * At least 4-6 weeks since prior 5-alpha-reductase inhibitor (e.g., finasteride) for benign prostatic hypertrophy Radiotherapy: * No prior pelvic irradiation Surgery: * No prior radical prostatectomy * Prior transurethral resection of the prostate allowed Other: * No prior cytotoxic anticancer therapy * No other prior treatment for prostate cancer * No other concurrent anticancer therapy unless documented disease progression

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
• Eastern Cooperative Oncology Group: collaborator
• SWOG Cancer Research Network: collaborator
• Medical Research Council: collaborator

Study Sites (15)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Regional Cancer Program of the Hopital Regional

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

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, 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

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (3)

• Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC CTG PR.3/MRC UK PR07 investigators. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. doi: 10.1016/S0140-6736(11)61095-7. Epub 2011 Nov 2.

  PMID: 22056152 RESULT

• Brundage M, Sydes MR, Parulekar WR, Warde P, Cowan R, Bezjak A, Kirkbride P, Parliament M, Moynihan C, Bahary JP, Parmar MK, Sanders K, Chen BE, Mason MD. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial. J Clin Oncol. 2015 Jul 1;33(19):2151-7. doi: 10.1200/JCO.2014.57.8724. Epub 2015 May 26.

  PMID: 26014295 DERIVED

• Mason MD, Parulekar WR, Sydes MR, Brundage M, Kirkbride P, Gospodarowicz M, Cowan R, Kostashuk EC, Anderson J, Swanson G, Parmar MK, Hayter C, Jovic G, Hiltz A, Hetherington J, Sathya J, Barber JB, McKenzie M, El-Sharkawi S, Souhami L, Hardman PD, Chen BE, Warde P. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer. J Clin Oncol. 2015 Jul 1;33(19):2143-50. doi: 10.1200/JCO.2014.57.7510. Epub 2015 Feb 17.

  PMID: 25691677 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Buserelin; Flutamide; Goserelin; Leuprolide; nilutamide; Orchiectomy; Radiotherapy

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; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Castration; Endocrine Surgical Procedures; Surgical Procedures, Operative; Urogenital Surgical Procedures; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Therapeutics

Study Officials

• Padraig R. Warde, MB, MRCPI, FRCPC

  Princess Margaret Hospital, Canada

  STUDY CHAIR

• Richard R. Whittington, MD

  Abramson Cancer Center at Penn Medicine

  STUDY CHAIR

• Srinivasan Vijayakumar, MD

  Michael Reese Hospital and Medical Center

  STUDY CHAIR

• Patricia Lillis-Hearne, MD

  Brooke Army Medical Center

  STUDY CHAIR

• Malcolm D. Mason, MD

  Velindre NHS Trust

  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: February 8, 1995
• Primary Completion: September 23, 2011
• Study Completion: January 6, 2012
• Last Updated: April 3, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (15)