Stereotactic Body Radiation Therapy in Treating Patients With Prostate Cancer

A Phase I and II Study of Stereotactic Body Radiation Therapy (SBRT) for Low and Intermediate Risk Prostate Cancer (SBRT Prostate)

RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: stereotactic body radiation therapy (SBRT)- 45 Gy; Radiation: stereotactic body radiation therapy (SBRT) - 47.5 Gy; Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 1); Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2)

Detailed Description

OBJECTIVES:

Primary

• To escalate the dose of stereotactic body radiotherapy (SBRT) to a tumoricidal dose without exceeding the maximum tolerated dose in patients with organ-confined prostate cancer. (Phase I)
• To determine the late, severe grade 3-5 genitourinary and gastrointestinal toxicity occurring between 270-540 days (i.e., 9-18 months) from the start of the protocol treatment as assessed by CTCAE v3.0. (Phase II)

Secondary

• To determine the dose-limiting toxicity of SBRT in these patients. (Phase I)
• To determine the 2-year biochemical (PSA) control (freedom from PSA failure), disease-free and overall survival, local control, freedom from distant metastases, and the incidence of high-grade adverse events of any type in patients treated with this therapy in order to determine if the therapy is promising enough for further clinical investigation. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II open-label study.

• Phase I: Patients undergo 5 treatments of stereotactic body radiotherapy (SBRT).
• Phase II: Patients undergo SBRT at the maximum tolerated dose as in phase I. After completion of study treatment, patients are followed at 1.5, 3, 6, 9, and 12 months, every 6 months for 5 years, and then once a year for years 5-10.

PROJECTED ACCRUAL: A total of 97 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
  • Florida
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando Florida
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center at University of Minnesota
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Stage T1a, T1b, T1c disease
  • Stage T2a or T2b
• No direct evidence of regional or distant metastases
• No T2c, T3, or T4 tumors
• Gleason score ≤ 7

• Must meet the following criteria:

  • Prostate-specific antigen (PSA) ≤ 20 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 2-6
  • PSA ≤ 15 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 7
  • Risk of pelvic lymph node involvement < 20% according to Roach formula
• Ultrasound-based volume estimation of the prostate gland ≤ 60 g

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Fertile patients must use effective contraception
• No prior invasive malignancy, except for nonmelanoma skin cancer, unless disease-free for a minimum of 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are allowed)

• No significant urinary obstructive symptoms

  • American Urological Association (AUA) score of ≤ 15 (alpha blockers allowed)
• No history of inflammatory colitis (including Crohn disease and ulcerative colitis)
• No history of significant psychiatric illness

• No severe, active comorbidity including any of the following:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration

  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

    • Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

  • AIDS (based on current CDC definition) or other immunocompromising condition

    • HIV testing is not required for entry into this protocol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 9 months since prior hormonal therapy as neoadjuvant therapy or to downsize the prostate gland
• No prior pelvic radiotherapy
• No prior chemotherapy or surgery for prostate cancer
• No prior transurethral resection of the prostate (TURP) or cryotherapy to the prostate
• No plans for other concurrent post-treatment, adjuvant, antineoplastic therapy including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy as part of the treatment for prostate cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT) 45 Gy; The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated - 45 Gy	Radiation: stereotactic body radiation therapy (SBRT)- 45 Gy; Dose of SBRT - 45 Gray (Gy) in five fractions
Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT)- 47.5 Gy; The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated- 47.5 Gy	Radiation: stereotactic body radiation therapy (SBRT) - 47.5 Gy; Dose of SBRT - 47.5 Gray (Gy) in five fractions; Other Names: Dose of SBRT - 47.5 Gy in five fractions
Experimental: Phase 1: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy; The Phase 1 portion of the study will have a 3+3 design. The dose of SBRT is escalated- 50 Gy	Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 1); Other Names: Dose of SBRT - 50 Gray (Gy) in five fractions
Experimental: Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy; The dose of SBRT is escalated - 50 Gy in Phase 2	Radiation: stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2); Other Names: Dose of SBRT - 50 Gray (Gy) in five fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (Phase 1 Only)	Dose-limiting toxicity (DLT) was defined as grade 3 to 5 GI, genito urinary, sexual, or neurologic toxicity attributed to therapy occurring within 90 days of registration using Common Terminology Criteria of Adverse Events(version 3)	90 days after start of treatment
No. of Late Severe GU Toxicity (for Phase 2 Only)	To determine late severe GU toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	18 months
No. of Late Severe GI Toxicity (for Phase 2 Only)	To determine late severe GI toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GU Toxicity (Only Phase 2)	To determine acute severe GU toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	9 months from start of treatment
GI Toxicity	To determine acute severe GI toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	9 months from start of treatment
Non-GU Toxicity	To determine non-GU (genitourinary) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	60 months
Non-GI Toxicity	To determine non-GI (gastrointestinal) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.	60 months
Freedom From Biochemical Failure	Biochemical failure RTOG (Radiation Therapy Oncology Group)-ASTRO (American Society for Therapeutic Radiology and Oncology) definition (also known as Phoenix definition). Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached.	36 months
Overall Survival	The survival time will be measured from the date of accession to the date of death.	60 months
Disease Specific Survival	Disease-Specific Survival Disease-specific survival will be measured from the date of study entry to the date of death due to prostate cancer as the percentage of participants who survived the prostrate cancer disease.	60 months
Clinical Progression Including Local/Regional and Distant Relapse	Clinical progression including local/regional and distant relapse is measured using Kaplan-Meier method	60 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Study Chair: Robert D. Timmerman, MD, Simmons Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2006
• Primary Completion (Actual): July 20, 2014
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: October 19, 2007
• First Submitted That Met QC Criteria: October 19, 2007
• First Posted (Estimate): October 22, 2007

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: adenocarcinoma of the prostate; stage I 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
• Other Study ID Numbers: SCCC-0604122; STU 072010-019; SCCC-062006-010; CDR0000571546 (Registry Identifier: PDQ (Physician Data Query)); UMN-2006UC048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No