A Phase I/II Study of High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Stanford University
- Enrollment
- 146
- Locations
- 2
- Primary Endpoint
- Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v3.0
Study Overview
Brief Summary
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- Male
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Triptorelin Pamoate (Drug)
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.
Intervention: Degarelix (Drug)
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.
Intervention: Internal Radiation Therapy (Radiation)
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.
Intervention: Laboratory Biomarker Analysis (Other)
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.
Intervention: Quality-of-Life Assessment (Other)
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.
Intervention: Leuprolide Acetate (Drug)
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.
Intervention: Goserelin Acetate (Drug)
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.
Intervention: Bicalutamide (Drug)
Outcomes
Primary Outcomes
Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v3.0
Time Frame: Within 6 months of HDR completion
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.
Secondary Outcomes
- Proportion of men with a nPSA12 of < 2 ng/mL(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(From the completion of all treatment to the time of BF, assessed at 5 years)
- Change in quality of life as measured by EPIC scores(Baseline to up to 5 years)
- Cost-effectiveness of HDR BT as monotherapy for prostate cancer using as measured by EQ-5D scores(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)(Baseline)
- Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v4.0(Within 6 months of HDR completion)
- Late GU toxicity, scored according to CTCAE v3.0 and v4.0(Up to 5 years)
- Acute GI toxicity scored according to CTCAE v3.0 and CTCAE v4.0(Up to 6 months after completing HDR BT)
- Late GI toxicity, scored according to CTCAE v3.0 and CTCAE v4.0(Up to 5 years)
- Dosimetric predictors of toxicity (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(Baseline to up to 5 years)
Investigators
Mark Buyyounouski
Professor of Radiation Oncology (Radiation Therapy)
Stanford University