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Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03570827
Recruitment Status : Active, not recruiting
First Posted : June 27, 2018
Last Update Posted : August 6, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE June 5, 2018
First Posted Date  ICMJE June 27, 2018
Last Update Posted Date August 6, 2020
Actual Study Start Date  ICMJE May 8, 2018
Estimated Primary Completion Date May 8, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
Freedom from failure (FF) defined as the first occurrence of clinical failure (local recurrence, regional recurrence, or distant metastasis), the start/re-start of salvage therapy including androgen suppression, and biochemical failure (PSA >= 0.5 ng/ml) [ Time Frame: Up to 5 years ]
Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
  • Acute grade 2 or higher and grade 3 or higher genitourinary (GU) and gastrointestinal (GI) toxicity performed using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria [ Time Frame: Up to 5 years ]
    Descriptive measurements of frequency will be compiled. The maximum grade for each type of acute adverse events (AE) will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Similarly, grade 3 or higher GU and GI events will be estimated along with overall toxicity.
  • Grade 2 or higher and grade 3 or higher GI and GU toxicity performed using NCI-CTCAE version 4 criteria [ Time Frame: 3 years ]
    The maximum grade for each type of acute adverse events (AE) will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Similarly, grade 3 or higher GU and GI events will be estimated along with overall toxicity.
  • Local/distant failure [ Time Frame: Start of treatment assessed up to 5 years ]
    Will be measured from the date of the start of treatment to the date of documented local failure as determined either by clinical exam, imaging, or by prostate rebiopsy.
  • Distant metastasis [ Time Frame: Up to 5 years ]
    Will be assessed using AJCC STAGING SYSTEM- PROSTATE, 8TH EDITION
  • Quality of life (QOL) items from the Expanded Prostate Cancer Index Composite [ Time Frame: Up to 5 years ]
    Summation of relative scores for quality of life items from the Expanded Prostate Index Composite (EPIC) instrument will be used to measure each individual's quality of life. The difference in mean scores will be assessed with the t-test. To assess changes in health-related QOL from baseline, a clinically significant difference will be defined as half of a standard deviation (SD) and at least a 10-point change. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Analysis will include percent change from baseline using t-tests and generalized linear models to test for changes at each time point and non-zero slope respectfully. EPIC is a validated instrument that measures urinary, bowel, and sexual function and bother. To statistically evaluate change over time, responses will be grouped by system and assigned a numeric score. The difference in mean scores will be assessed with the t-test.
  • Impotence [ Time Frame: Up to 3 years ]
    Summation of relative scores for sexual function items (items 31 through 39) from the Expanded Prostate Index Composite (EPIC) instrument will be used to measure each individual's quality of life. Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate. EPIC is a validated instrument that measures urinary, bowel, and sexual function and bother. To statistically evaluate change over time, responses will be grouped by system and assigned a numeric score. The difference in mean scores will be assessed with the t-test.
  • Salvage androgen suppression use [ Time Frame: Up to 5 years ]
    Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate.
  • Overall survival [ Time Frame: Up to 5 years ]
    Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals (CIs).
  • Progression free survival [ Time Frame: Up to 5 years ]
    Will use clinical, biochemical and SAD as events. Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.
  • Disease-free survival [ Time Frame: Up to 5 years ]
    Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.
  • Freedom from biochemical failure (FFBF) [ Time Frame: Up to 5 years ]
    Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 25, 2018)
  • Development of quality assurance process for prostate proton therapy [ Time Frame: Up to 5 years ]
    Will perform physics check according to Sec 7.12 of protocol.
  • Pathologic and radiologic findings [ Time Frame: Up to 5 years ]
    Correlated with outcome (AJCC Criteria 8th Ed.- appendix II)
  • Estimation of prostate and normal structure movement [ Time Frame: Up to 5 years ]
    during radiation therapy (RT) with the use of scans. Data will be summarized by frequencies and mean (SD) or median values.
  • Dose volume relationship of normal structures with toxicity [ Time Frame: Up to 5 years ]
  • Potentially, future research of pathologic risk factors [ Time Frame: Up to 5 years ]
    Allow for future research of pathologic risk factors that may influence prognosis; this information will help us to attempt to characterize their presence in prostate cancer with high risk features after prostatectomy and their potential effect on outcomes.
  • Possible comparison of an intensity-modulated radiation therapy (IMRT) plan with the proton therapy radiation plan [ Time Frame: Up to 5 years ]
    Proton therapy and x-ray dosimetry levels will be compared to outcomes and described in Groups I/II and III separately. Data will be summarized by frequences and mean (SD) or median values. Continuous variable will be compared using unpaired t tests and nonimal variables will be compared using contingency tables and Chi square analyses.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy
Official Title  ICMJE A Phase II Trial of Hypofractionated Radiation Therapy for Prostate Cancer With High Risk Features After Radical Prostatectomy
Brief Summary This phase II trial studies how well hypofractionated radiation therapy works in treating participants with prostate cancer high-risk features following radical prostatectomy. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine if stereotactic body radiation therapy (SBRT) would result in similar freedom from failure (FFF) than standard fractionation photon therapy.

SECONDARY OBJECTIVES:

I. After completion of radiation therapy, determine the incidence of grade 2 or greater genitourinary (GU) and gastrointestinal (GI) toxicity at 6 months (Common Terminology Criteria for Adverse Events [CTCAE] version 4).

II. After completion of radiation therapy, determine the incidence of grade 3 or greater GU and GI toxicity at 6 months (CTCAE version 4).

III. After completion of radiation therapy, determine the incidence of quality of life issues following completion of radiation therapy.

IV. After completion of radiation therapy, determine the incidence of impotence after the use of radiation therapy at 3 years.

V. After completion of radiation therapy, determine the incidence of freedom from biochemical failure (FFBF) at 5 years.

VI. After completion of radiation therapy, determine the incidence of clinical failure: local and/or distant at 5 years.

VII. After completion of radiation therapy, determine the incidence of salvage androgen deprivation use (SAD) at 5 years.

VIII. After completion of radiation therapy, determine the incidence of progression free survival: using clinical, biochemical and SAD as events at 5 years.

IX. After completion of radiation therapy, determine the incidence of overall survival at 5 years.

X. After completion of radiation therapy, determine the incidence of disease-specific survival at 5 years.

XI. Determine the impact of radiation therapy on quality of life. XII. Determine overall GI and GU toxicity. XIII. Determine prostate and normal structure movement during radiation therapy (RT) with the use of scans.

XIV. Correlate pathologic and radiologic findings with outcomes. XV. Correlate pre-RT prostate specific antigen (PSA) levels with outcomes. XVI. Correlate variation in proton therapy or x-ray dosimetry and outcomes. XVII. Develop a quality assurance process for prostate proton therapy. XVIII. Prospectively collect information that will help to define dose-volume relationships of normal structures with acute and chronic toxicity.

XIX. Allow for future research of pathologic risk factors that may influence prognosis; this information will help us to attempt to characterize their presence in prostate cancer with high risk features after prostatectomy and their potential effect on outcomes.

XX. Possibly compare dosimetric parameters of an IMRT plan with the proton therapy radiation plan.

OUTLINE: Participants are assigned to 1 of 3 groups.

GROUP I: Participants undergo hypofractionated radiation therapy over 15-30 minutes every other day over 2 weeks, for 5 treatments.

GROUP II: Beginning 8-10 weeks before radiation therapy, participants receive androgen suppression therapy subcutaneously (SC) or intramuscularly (IM) for up to 6 months (at the discretion of the treating physician). Participants then undergo hypofractionated radiation therapy as Group I.

GROUP III: Participants receive androgen suppression therapy as Group II for up to 18 months (at the discretion of the treating physician), then undergo hypofractionated radiation therapy over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.

After completion of study treatment, participants are followed up at 3 and 12 months, every 6 months for 2 years, annually for 3 years, then biennially thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Adenocarcinoma
  • PSA Level Less Than Two
  • Stage IIB Prostate Cancer AJCC v8
  • Stage III Prostate Cancer AJCC v8
  • Stage IIIA Prostate Cancer AJCC v8
  • Stage IIIB Prostate Cancer AJCC v8
  • Stage IIIC Prostate Cancer AJCC v8
Intervention  ICMJE
  • Drug: Androgen Suppression
    Given androgen suppression therapy
    Other Names:
    • androgen ablation
    • androgen deprivation
  • Radiation: Hypofractionated Radiation Therapy
    Undergo hypofractionated radiation therapy
    Other Names:
    • Hypofractionated Radiotherapy
    • hypofractionation
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Experimental: Group I (hypofractionated radiation therapy)
    Participants undergo hypofractionated radiation therapy over 15-30 minutes every other day over 2 weeks, for 5 treatments.
    Interventions:
    • Radiation: Hypofractionated Radiation Therapy
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: Group II (radiation therapy, androgen suppression therapy)
    Beginning 8-10 weeks before radiation therapy, participants receive androgen suppression therapy SC or IM for up to 6 months (at the discretion of the treating physician). Participants then undergo hypofractionated radiation therapy as Group I.
    Interventions:
    • Drug: Androgen Suppression
    • Radiation: Hypofractionated Radiation Therapy
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: Group III (radiation therapy, androgen suppression therapy)
    Participants receive androgen suppression therapy as Group II for up to 18 months (at the discretion of the treating physician), then undergo hypofractionated radiation therapy over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.
    Interventions:
    • Drug: Androgen Suppression
    • Radiation: Hypofractionated Radiation Therapy
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 4, 2020)
52
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2018)
62
Estimated Study Completion Date  ICMJE May 8, 2023
Estimated Primary Completion Date May 8, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed prostate adenocarcinoma at the time of surgery
  • Pathologic stages T2-T3b, N0-Nx-N1, M0-1 as staged by the pathology report (American Joint Committee on Cancer [AJCC] criteria 8th edition [Ed.])
  • One or more high risk features including: seminal vesicle invasion, extracapsular extension, positive margins, or a PSA post surgery between 0.2 and < 2.0
  • PSA values < 2 ng/ml within 90 days prior to enrollment. Obtained at least 6 weeks after surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 assessed within 90 days of enrollment
  • Patients must sign Institutional Review Board (IRB) approved study specific informed consent
  • Patients must complete all required pre-entry tests within the specified time frames
  • Patients must be able to start treatment (androgen suppression [AS] or radiation) within 120 days of study registration
  • Positron emission tomography (PET) scan is suggested for a PSA >= 0.2 ngs/ml
  • Magnetic resonance imaging (MRI) pelvis, computed tomography (CT) pelvic, or bone scan for a PSA >= 0.2 ngs/ml may be done, based on the physician preference
  • Members of all races and ethnic groups are eligible for this trial
  • Patients from outside of the United States may participate in the study

Exclusion Criteria:

  • Previous pelvic radiation
  • Prior androgen suppression therapy for prostate cancer for more than 6 months
  • Active rectal diverticulitis, Crohn?s disease affecting the rectum or ulcerative colitis (non-active diverticulitis and Crohn?s disease not affecting the rectum are allowed)
  • Prior systemic chemotherapy for prostate cancer
  • History of proximal urethral stricture requiring dilatation
  • Current and continuing anticoagulation with warfarin sodium (coumadin), heparin, low- molecular weight heparin, Clopidogrel bisulfate (plavix), or equivalent (unless it can be stopped to manage treatment related toxicity, to have a biopsy if needed, or place markers)
  • Major medical, addictive or psychiatric illness which in the investigator?s opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up. (Consent by legal authorized representative is not permitted for this study)
  • Evidence of any other cancer within the past 5 years and < 50% probability of a 5 year survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell cancer of the skin is allowed)
  • History of myocardial infarction or decompensated congestive heart failure (CHF) within the last 6 months
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03570827
Other Study ID Numbers  ICMJE MC1754
NCI-2018-00943 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1754 ( Other Identifier: Mayo Clinic in Arizona )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Carlos Vargas Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP