Clinical Trials /

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

NCT03274687

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer
  • Official Title: A Randomized Phase III Trial of Hypofractionated Post-prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-prostatectomy Radiation Therapy (COPORT)

Clinical Trial IDs

  • ORG STUDY ID: NRG-GU003
  • SECONDARY ID: NCI-2016-01771
  • SECONDARY ID: NRG-GU003
  • SECONDARY ID: NRG-GU003
  • SECONDARY ID: NRG-GU003
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03274687

Conditions

  • Prostate Adenocarcinoma
  • Stage I Prostate Adenocarcinoma
  • Stage II Prostate Adenocarcinoma
  • Stage III Prostate Adenocarcinoma

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (conventional radiation therapy)ExperimentalPatients 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 (hypofractionated radiation therapyExperimentalPatients 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.

      Eligibility 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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Male
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Change in score for the GI domain of the EPIC
      Time Frame:Baseline to 2 years
      Safety Issue:
      Description: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

      Measure: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
      Safety Issue:
      Description: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.
      Measure: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
      Safety Issue:
      Description:Will be estimated by the Kaplan-Meier method.
      Measure:Incidence of adverse events (AEs) evaluated according to Common Terminology Criteria for Adverse Events version 4.0
      Time Frame:Up to 5 years
      Safety Issue:
      Description: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.
      Measure: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.
      Safety Issue:
      Description: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.
      Measure:Overall Survival Rates
      Time Frame:From date of randomization to death, assessed up to 5 years
      Safety Issue:
      Description: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.
      Measure:Patient-reported GI symptoms assessed using the EPIC
      Time Frame:Up to 5 years
      Safety Issue:
      Description: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.
      Measure:Patient-reported GU symptoms assessed using the EPIC
      Time Frame:Up to 5 years
      Safety Issue:
      Description: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.
      Measure: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
      Safety Issue:
      Description: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.
      Measure: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
      Safety Issue:
      Description: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.
      Measure: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
      Safety Issue:
      Description: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.

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:NRG Oncology

      Last Updated

      December 22, 2017