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Trial record 1 of 1 for:    03274687
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Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer

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: NCT03274687
Recruitment Status : Active, not recruiting
First Posted : September 7, 2017
Results First Posted : June 6, 2022
Last Update Posted : June 28, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Study Description
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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 Phase
Prostate Adenocarcinoma Stage I Prostate Adenocarcinoma Stage II Prostate Adenocarcinoma Stage III Prostate Adenocarcinoma Radiation: Hypofractionated radiation therapy Radiation: Conventional radiation therapy Drug: Optional androgen deprivation therapy Phase 3

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.

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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 296 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
Actual Primary Completion Date : December 1, 2020
Estimated Study Completion Date : November 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Conventional radiation therapy
Conventional post-prostatectomy radiation therapy (COPORT) over 7 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation.
 Radiation: Conventional radiation therapy
62.5 Gy in 25 daily fractions of 2.5 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.

Drug: Optional androgen deprivation therapy
Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.
Other Name: ADT
Experimental: Hypofractionated radiation therapy
Hypofractionated post-prostatectomy radiation therapy (HYPORT) over 5 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation.
 Radiation: Hypofractionated radiation therapy
66.6 Gy in 37 daily fractions of 1.8 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.
Other Names:
  • Hypofractionated Radiotherapy
  • hypofractionation

Drug: Optional androgen deprivation therapy
Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.
Other Name: ADT


Outcome Measures
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Primary Outcome Measures :
  1. Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years [ Time Frame: Baseline (randomization), 2 years ]
    The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.

  2. Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years [ Time Frame: Baseline, 2 years ]
    The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.


Secondary Outcome Measures :
  1. Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years [ Time Frame: Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT. ]
    The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.

  2. Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years [ Time Frame: Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT. ]
    The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.

  3. Percentage of Participants With Biochemical Failure [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. ]
    Biochemical failure was analyzed using two different definitions. The protocol definition of biochemical failure is a PSA measurement ≥ 0.4 ng/mL and rising (i.e. PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount) or followed by initiation of salvage hormones. The Phoenix definition of biochemical failure is a PSA measurement ≥ PSA nadir + 2 ng/mL where nadir is the lowest post-RT PSA value. Time to biochemical failure is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.

  4. Percentage of Participants With Progression [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Progression (failure) is defined as the first occurrence of biochemical failure, local failure, regional failure, distant failure, institution of new unplanned anticancer treatment, or death from prostate cancer. Time to progression is defined as time from randomization to the date of progression, last known follow-up (censored), or death without progression (competing risk). Progression rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.

  5. Percentage of Participants With Local-Regional Failure [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Local-regional failure is defined as local or regional failure. Local failure is defined as the development of a new biopsy-proven mass in the prostate bed. Regional failure is defined as radiographic evidence (CT or MRI) of lymphadenopathy (lymph node size ≥ 1.0 cm in the short axis) in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy. Time to local-regional failure is defined as time from randomization to the date of first local-regional failure, last known follow-up (censored), or death without local-regional (competing risk). Local-regional failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.

  6. Percentage of Participants Receiving Salvage Therapy [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Salvage therapy is defined as the initiation of new unplanned anticancer treatment. Time to salvage therapy initiation is defined as time from randomization to the date of first salvage therapy, last known follow-up (censored), or death without salvage therapy (competing risk). Salvage therapy rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage initiation times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.

  7. Percentage of Participants With Distant Metastasis [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Distant metastasis (failure) is defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI. Time to distant metastasis is defined as time from randomization to the date of first distant metastasis, last known follow-up (censored), or death without local recurrence (competing risk). Distant metastasis rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.

  8. Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Cause of death was centrally reviewed. Count and percentage at time of analysis are reported.

  9. Percent of Participants Alive (Overall Survival) [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Overall survival time is defined as time from registration/randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 2-year rates are provided.

  10. Number of Participants With Grade 3+ Adverse Events [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. ]
    Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event, any grade 3 or higher gastrointestinal adverse events, and any grade 3 or higher genitourinary adverse events are reported. Adverse events of any attribution are included.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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 CD4 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
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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


Locations
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Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mark Buyyounouski NRG Oncology
  Study Documents (Full-Text)

Documents provided by NRG Oncology:
Study Protocol and Statistical Analysis Plan  [PDF] April 26, 2019
Informed Consent Form  [PDF] April 26, 2019

More Information
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03274687    
Other Study ID Numbers: NRG-GU003
NCI-2016-01771 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GU003
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
Results First Posted: June 6, 2022
Last Update Posted: June 28, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
 Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs