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Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03274687
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : December 27, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This randomized phase III trial studies how well hypofractionated radiation therapy works compared to conventional radiation therapy after surgery in treating patients with prostate cancer. 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. Conventional radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. It is not yet known whether giving hypofractionated radiation therapy or conventional radiation therapy after surgery may work better in treating patients with prostate cancer.

Condition or disease Intervention/treatment
Prostate Adenocarcinoma Stage I Prostate Adenocarcinoma Stage II Prostate Adenocarcinoma Stage III Prostate Adenocarcinoma Radiation: Hypofractionated Radiation Therapy Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Radiation: Radiation Therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point.

SECONDARY OBJECTIVES:

I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of treatment.

II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and 60 months from end of treatment.

III. To compare the cost effectiveness based on the cost of radiotherapy and measured utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D).

IV. To compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (prostate cancer specific mortality [PCSM]).

V. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate prostate specific antigen (PSA) >= PSA nadir + 2 ng/mL definition of BF.

VI. To compare local failure, regional failure, salvage therapy (i.e. institution of new unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates.

VII. Assessment of adverse events. VIII. Paraffin-embedded tissue block, serum, plasma, whole blood, and urine for future translational research analyses for predictors of toxicity following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo conventional radiation therapy for 37 fractions over 7 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.

ARM II: Patients undergo hypofractionated radiation therapy for 25 fractions over 5 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.

After completion of study treatment, patients are followed up every 6 months for 2 years and every year for 3 years and thereafter.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of Hypofractionated Post-prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-prostatectomy Radiation Therapy (COPORT)
Actual Study Start Date : July 28, 2017
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : July 31, 2026

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Arm I (conventional radiation therapy)
Patients undergo conventional radiation therapy for 37 fractions over 7 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo conventional radiation therapy
Experimental: Arm II (hypofractionated radiation therapy
Patients undergo hypofractionated radiation therapy for 25 fractions over 5 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.
Radiation: Hypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy
Other Names:
  • Hypofractionated Radiotherapy
  • hypofractionation
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment


Outcome Measures

Primary Outcome Measures :
  1. Change in score for the GI domain of the EPIC [ Time Frame: Baseline to 2 years ]
    Will be analyzed using a t-test with a significance level of 0.025. If the data are determined to be non-normal, a Wilcoxon test may be used instead. Missing data will be assessed.

  2. Change in score for the total GU domain (combined urinary incontinence and urinary irritative/obstructive scales) of the EPIC [ Time Frame: Baseline to 2 years ]
    Will be analyzed using a t-test with a significance level of 0.025. If the data are determined to be non-normal, a Wilcoxon test may be used instead. Missing data will be assessed.


Secondary Outcome Measures :
  1. Distant Metastasis (DM) defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI [ Time Frame: From the date of randomization to the date of documented DM, assessed up to 5 years ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Fine and Gray's regression will be used. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.

  2. Freedom From Biochemical Failure (FFBF) where biochemical failure is defined as a PSA >= 0.4 ng/mL and rising. [ Time Frame: Up to 5 years ]
    Will be estimated by the Kaplan-Meier method.

  3. Incidence of adverse events (AEs) evaluated according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
    Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. A Chi-square test will be used to compare the number of patients with at least 1 grade 3 or higher AE between the treatment arms. A comparison of grade 3 and higher GU and GI events related to treatment (separately) between treatment arms will also be tested using a Chi-square test.

  4. Local failure defined as the development of a new biopsy-proven mass in the prostate bed after enrollment in the protocol [ Time Frame: From the date of randomization to the date of documented local failure, assessed up to 5 years. ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Fine and Gray's regression will be used. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.

  5. Overall Survival Rates [ Time Frame: From date of randomization to death, assessed up to 5 years ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Cox regression will be used to obtain HRs. Will be estimated by the Kaplan-Meier method. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.

  6. Patient-reported GI symptoms assessed using the EPIC [ Time Frame: Up to 5 years ]
    The change scores will be analyzed using a t-test. If the data are determined to be non-normal, a Wilcoxon test may be used instead. A longitudinal analysis incorporating all follow-up time points will be conducted using a general linear model with maximum likelihood estimation, adjusting for baseline domain score, treatment arm, Gleason score, baseline PSA, T-stage, age, and race. If found to significantly differ between arms, then analysis of the function and bother subscales will be undertaken to assess which particular subscale is driving the significant difference.

  7. Patient-reported GU symptoms assessed using the EPIC [ Time Frame: Up to 5 years ]
    The change scores will be analyzed using a t-test. If the data are determined to be non-normal, a Wilcoxon test may be used instead. A longitudinal analysis incorporating all follow-up time points will be conducted using a general linear model with maximum likelihood estimation, adjusting for baseline domain score, treatment arm, Gleason score, baseline PSA, T-stage, age, and race. If found to significantly differ between arms, then analysis of the incontinency and irritative/obstructive subscales will be undertaken to assess which particular subscale is driving the significant difference.

  8. Prostate Cancer Specific Mortality (PCSM) [ Time Frame: From the date of randomization to the date of death due to prostate cancer, assessed up 5 years ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Fine and Gray's regression will be used. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.

  9. Regional failure defined as radiographic evidence of lymphadenopathy in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy evaluated by CT or MRI [ Time Frame: From the date of randomization to the date of documented regional metastasis, assessed up to 5 years ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Fine and Gray's regression will be used. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.

  10. Time To Progression (TTP) where progression is defined as the first occurrence of biochemical failure, local failure, regional failure, DM, institution of new unplanned anticancer treatment, or death from prostate cancer [ Time Frame: Up to 5 years ]
    Will treat death as a competing risk and will be estimated by the cumulative incidence method. Cox regression will be used to obtain hazard ratios (HRs). Fine and Gray's regression will be used. Adjusted HRs and the respective 95% confidence interval will be computed. Baseline PSA, stratification variables (baseline EPIC-26 score and ADT status), and, as appropriate, age, race, and other covariates (Gleason, T-stage), will be adjusted for in this analysis. Statistical power will be limited for these analyses.


Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION
  • Adenocarcinoma of the prostate treated primarily with radical prostatectomy

    • Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy
  • One of the following pathologic T-classifications: pT2 or pT3

    • Patients with positive surgical margins are eligible
  • One of the following pathologic N-classifications: pN0, pNX

    • If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible
  • No clinical evidence of regional lymph node metastasis

    • Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration
    • Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1 cm in the short axis
  • A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL
  • No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration

    • Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass
    • Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor
  • No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration

    • Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis
  • Zubrod performance status 0-1 within 60 days prior to step 1 registration
  • The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
  • Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire
  • Only English and French-speaking patients are eligible to participate
  • PRIOR TO STEP 2 REGISTRATION
  • The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization

Exclusion Criteria:

  • A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7
  • pT2 with a negative surgical margin and PSA < 0.1 ng/mL
  • Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration;

    • Note: The use of finasteride or dutasteride (? tamsulosin) for longer periods prior to prostatectomy is acceptable
  • Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days)
  • Neoadjuvant chemotherapy before or after prostatectomy
  • Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed
  • Previous chemotherapy for any other disease site if given within 3 years prior to step 1
  • Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration
    • Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
    • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
    • End-stage renal disease (ie, on dialysis or dialysis has been recommended)
  • Prior allergic reaction to the study drugs involved in this protocol
  • History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274687


  Show 153 Study Locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Buyyounouski NRG Oncology
More Information

Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03274687     History of Changes
Other Study ID Numbers: NRG-GU003
NCI-2016-01771 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GU003 ( Other Identifier: NRG Oncology )
NRG-GU003 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: December 27, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases