High-Dose Brachytherapy in Treating Patients With Prostate Cancer

A Phase I/II Study of High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

This trial studies the side effects and how well high-dose brachytherapy works in treating patients with prostate cancer that has not spread to other parts of the body. Brachytherapy is a type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor and may be a better treatment in patients with prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma; Stage I Prostate Cancer; Stage III Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Bicalutamide; Drug: Goserelin Acetate; Drug: Degarelix; Radiation: Internal Radiation Therapy; Drug: Leuprolide Acetate; Drug: Triptorelin Pamoate

Detailed Description

PRIMARY OBJECTIVES:

To estimate the rate of acute (within 6 months of high-dose rate [HDR] completion) grade ≥ 2 genitourinary (GU) toxicity following high-dose-rate (HDR) brachytherapy (BT) as monotherapy for newly-diagnosed prostate cancer using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3 (CTCAE v3.0).

SECONDARY OBJECTIVES:

• Estimate the proportion of men with a prostate-specific antigen (PSA) nadir by one year (nPSA12) of < 2 ng/mL.
• Estimate the rate of freedom from biochemical failure at 5 years (FFBF).
• Evaluate patient-reported quality of life via the 32-item Expanded Prostate Cancer Index Composite (EPIC).
• Assess the cost-effectiveness of HDR BT as monotherapy for prostate cancer using the 6-item European Quality of Life 5-Dimensions (EQ-5D).
• Explore pre-treatment clinical risk factors to optimize patient selection for HDR BT as monotherapy for prostate cancer.
• Compare acute and late (> 6 months after HDR completion) GU and gastrointestinal (GI) grade ≥ 2 toxicity using CTCAE v3.0 and v4.0.
• Explore dosimetric predictors of toxicity.

Patients undergo high-dose-rate brachytherapy over 2 fractions. Patients may receive androgen deprivation therapy (ADT) comprising bicalutamide orally (PO) once daily (QD). Patients may also receive luteinizing hormone-releasing hormone (LHRH) agonist therapy comprising leuprolide acetate intramuscularly (IM) or subcutaneously (SC), goserelin acetate SC, triptorelin pamoate IM, or degarelix SC for 4 to 6 months (intermediate-risk patients receiving ADT) or 6 to 36 months (high-risk patients) at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and then yearly for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented pathologic confirmation of prostate adenocarcinoma
• Clinical T-classification T1-3
• PSA < 150 ng/mL
• Gleason score 6-10
• Clinically negative lymph nodes as established by abdomino-pelvic CT. CT only for clinical classification of T3 (with contrast if renal function is acceptable; a non-contrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection. Patients with lymph nodes equivocal or questionable by imaging are eligible if those nodes are <1 cm in short axis diameter. [56]
• No evidence of bone metastases (M0) on bone scan, only for PSA >20 ng/mLor Gleason ≥8, (NaF PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if plain films and/or MRI are negative for definite metastases.
• American Urological Association Symptom Index (AUA SI) =< 20

Exclusion Criteria:

• Clinical T4 disease
• PSA >= 150 ng/mL
• AUA SI > 20
• History of radical prostatectomy, external beam radiotherapy (EBRT), or BT for prostate cancer
• Previous chemotherapy for any malignancy, if given within three years of registration
• History of rectal surgery
• History of rectal fistula
• History of inflammatory bowel disease

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last six months
  • Transmural myocardial infarction within the last six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (HDR brachytherapy, ADT and LHRH agonist therapy); Patients undergo high-dose-rate brachytherapy over 2 fractions. Patients also receive ADT comprising bicalutamide PO QD. Patients may also receive LHRH agonist therapy comprising leuprolide acetate IM or SC, goserelin acetate SC, triptorelin pamoate IM, or degarelix SC for 4-6 months (intermediate-risk patients receiving ADT) or 6-36 months (high-risk patients) at the discretion of the treating physician.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Bicalutamide; Given PO; Other Names: CDX; Drug: Goserelin Acetate; Given SC; Other Names: ICI-118630; ZDX; Zoladex; Drug: Degarelix; Given SC; Other Names: Firmagon; FE200486; Radiation: Internal Radiation Therapy; Undergo high-dose-rate brachytherapy; Other Names: Internal Radiation; Internal Radiation Brachytherapy; Radiation Brachytherapy; Brachytherapy; Drug: Leuprolide Acetate; Given IM or SC; Other Names: A-43818; Drug: Triptorelin Pamoate; Given IM; Other Names: Trelstar; Pamorelin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v3.0	Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.	Within 6 months of HDR completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of men with a nPSA12 of < 2 ng/mL	nPSA12 is defined as the lowest PSA level achieved during the first year after completing HDR.	Up to 1 year after completion of HDR
FFBF (Biochemical failure define according to PSA nadir+2ng/mL and 3 consecutive rises definition according to American Society of Radiation Oncology	Biochemical failure (BF) will be defined according the PSA nadir + 2 ng/mL and three consecutive rises definition according to the American Society of Radiation Oncology consensus recommendation. Time to first BF will be analyzed with competing risk models with death as a competing risk.	From the completion of all treatment to the time of BF, assessed at 5 years
Cost-effectiveness of HDR BT as monotherapy for prostate cancer using as measured by EQ-5D scores	Measured utility values for each patient on this study will be combined with overall survival to calculate the "QALY" quality-adjusted life years.	Up to 5 years
Pre-treatment clinical risk factors to optimize patient selection for HDR BT as monotherapy for prostate cancer (association between each risk factor and the risk of having a first BF)	Clinical risk factors will be tested in competing risk models to evaluate the association between each risk factor and the risk of having a first BF.	Baseline
Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v4.0	Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.	Within 6 months of HDR completion
Late GU toxicity, scored according to CTCAE v3.0 and v4.0	Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.	Up to 5 years
Acute GI toxicity scored according to CTCAE v3.0 and CTCAE v4.0	Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.	Up to 6 months after completing HDR BT
Late GI toxicity, scored according to CTCAE v3.0 and CTCAE v4.0	Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.	Up to 5 years
Dosimetric predictors of toxicity (Doses to pelvic structures will be calculated and reviewed to determine possible correlations with toxicity outcomes)	Doses to pelvic structures will be calculated and reviewed to determine possible correlations with toxicity outcomes.	Up to 5 years
Change in Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Scores	The Expanded Prostate Cancer Index Composite (EPIC) is a patient-reported health-related quality of life questionnaire that evaluates urinary, bowel, sexual, and hormonal function and bother among patients undergoing treatment for prostate cancer. Higher scores indicate better health-related quality of life within each domain.	Baseline to up to 5 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Buyyounouski, Stanford University Hospitals and Clinics

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2015
• Primary Completion (Actual): December 14, 2021
• Study Completion (Actual): May 17, 2026

Study Registration Dates

• First Submitted: January 20, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimated): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; Radiotherapy; Gonadotropin-Releasing Hormone; Leuprolide; Goserelin; Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Brachytherapy; bicalutamide
• Other Study ID Numbers: IRB-32058; NCI-2015-00089 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); PROS0065 (Other Identifier: OnCore)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No