Adjuvant Radiation Therapy Plus Hormone Therapy Compared With Radiation Therapy Alone in Treating Patients With Stage II or Stage III Prostate Cancer

Phase III Randomized Study of Adjuvant Therapy for High Risk pT3N0 Prostate Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Drugs such as, flutamide or bicalutamide may stop the adrenal glands from producing androgens. Giving radiation therapy with hormone therapy after surgery to remove the tumor may kill any tumor cells remaining after surgery and be an effective treatment for stage II or stage III prostate cancer. It is not yet known if radiation therapy combined with hormone therapy is more effective than either radiation therapy alone or hormone therapy alone in treating stage II or stage III prostate cancer. (Hormone therapy alone group closed as of 12/9/2002.)

PURPOSE: Randomized phase III trial to compare the effectiveness of adjuvant radiation therapy plus hormone therapy to that of radiation therapy alone or hormone therapy alone in treating patients who have stage II or stage III prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: flutamide; Drug: bicalutamide; Drug: releasing hormone agonist therapy

Detailed Description

OBJECTIVES:

• Compare the overall survival, disease-free survival, freedom from distant metastases, and freedom from PSA failure in patients with high-risk stage II or III prostate cancer treated in the adjuvant setting with radiotherapy and hormonal therapy vs radiotherapy alone.
• Compare the qualitative and quantitative toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to seminal vesicle invasion (yes vs no), preoperative PSA (10 ng/mL or less vs greater than 10 ng/mL), Gleason score (2-6 vs 7 vs 8-10), positive surgical margins (yes vs no), and neoadjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm III closed to accrual as of 12/9/2002.)

• Arm I: Patients undergo radiotherapy once daily 5 days a week for 7 weeks. Beginning the first day of radiotherapy, patients also receive hormonal therapy comprising a luteinizing-hormone-releasing hormone agonist once every 1-4 months for 2 years AND oral flutamide 3 times daily OR oral bicalutamide once daily for 1 month.
• Arm II: Patients undergo radiotherapy as in arm I.
• Arm III (Closed to accrual as of 12/9/2002):Patients receive hormonal therapy as in arm I.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,398 patients (699 per treatment arm) will be accrued for this study within 5 years. (Arm III closed to accrual as of 12/9/2002.)

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer

  • T2-3, N0, M0
  • No metastatic disease

• High-risk for PSA relapse as defined by Gleason score 7 or higher and ≥ 1 of the following OR Gleason score < 7 and ≥ 2 of the following:

  • Preoperative PSA > 10 ng/mL
  • Positive surgical margins
  • Seminal vesicle invasion
• Preoperative PSA ≤ 40.0 ng/mL
• Postoperative PSA ≤ 0.2 ng/mL

• Negative lymph node status by lymph node sampling or dissection

  • If lymph node status is unknown, must have < 5% risk of involvement by Roach formula

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 130,000/mm^3
• Hemoglobin ≥ 11.4 g/dL

Hepatic:

• ALT ≤ 3 times normal

Renal:

• Creatinine ≤ 2.5 mg/dL

Other:

• No other prior or concurrent invasive malignancy within the past 5 years except superficial nonmelanoma skin cancer
• No other major medical or psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• At least 60 days since prior finasteride
• At least 90 days since prior testosterone
• Prior pharmacologic androgen ablation for prostate cancer allowed if initiated within the past 10 months (must switch to study ablation therapy OR discontinue therapy if randomized to receive radiotherapy only)

Radiotherapy:

• No prior radiotherapy to the pelvis
• No concurrent intensity-modulated radiotherapy

Surgery:

• No prior orchiectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LH-RH agonist plus radiation therapy; Luteinizing hormone-releasing hormone (LH-RH) agonist x 2 years plus radiation therapy (RT) to 63.0 - 66.6 Gy	Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: flutamide; Drug: bicalutamide; Drug: releasing hormone agonist therapy
Active Comparator: Radiation therapy alone; Radiation therapy alone to 63.0 - 66.6 Gy	Radiation: radiation therapy; Procedure: adjuvant therapy
Active Comparator: LH-RH agonist alone; Luteinizing hormone-releasing hormone (LH-RH) agonist x 2 years	Procedure: adjuvant therapy; Drug: flutamide; Drug: bicalutamide; Drug: releasing hormone agonist therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	From the date of randomization to the date of death due to any cause

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease-Free Survival	From the date of randomization to the date of first documented local progression or distant failure
Distant Failure	From the date of randomization to the date of frist documented metastatic disease
Biochemical Failure (detectable PSA)	From the date of randomization to the date of developing a PSA of 0.5 ng/ml or greater over the entry PSA

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NCIC Clinical Trials Group
• Investigators: Study Chair: Richard K. Valicenti, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University; Study Chair: Richard Choo, MD, Toronto Sunnybrook Regional Cancer Centre

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): June 1, 2004
• Study Completion (Actual): June 1, 2004

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Hormones; Bicalutamide; Flutamide
• Other Study ID Numbers: RTOG-P-0011; CDR0000068868; CAN-NCIC-PR9