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Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01368588
Recruitment Status : Active, not recruiting
First Posted : June 8, 2011
Last Update Posted : June 26, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Tracking Information
First Submitted Date  ICMJE June 7, 2011
First Posted Date  ICMJE June 8, 2011
Last Update Posted Date June 26, 2019
Actual Study Start Date  ICMJE July 2011
Estimated Primary Completion Date July 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
Overall Survival [ Time Frame: From date of randomization to the date of death. ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2011)
Overall survival of patients treated with NADT and RT vs NADT and WPRT
Change History Complete list of historical versions of study NCT01368588 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
  • Cause-specific survival [ Time Frame: From date of randomization to the date of death due to prostate cancer. ]
  • Distant metastasis-free survival [ Time Frame: From date of randomization to the date of first documented distant metastasis or date of first clinical and/or radiographic appearance of disseminated disease. ]
  • Biochemical failure by the Phoenix definition (PSA ≥ 2 ng/mL over the nadir PSA) [ Time Frame: From date of randomization to the date of first biochemical failure by phoenix definition within 5 years of randomization. ]
  • Incidence of "acute" adverse events as assessed by the Common Toxicity Criteria for Adverse Effects (CTCAE) current version [ Time Frame: From protocol treatment start date to the date of first occurrence of worst severity of the adverse event </= 30 days from completion of radiation therapy. ]
  • Time to "late" grade 3+ adverse events as assessed by CTCAE current version [ Time Frame: From protocol treatment start date to the date of the first late grade 3+ adverse event occurring more than 30 days after the completion of radiation therapy. ]
  • Prostate cancer-specific HRQOL change as measured by the EPIC-26 (bowel or urinary domain) [ Time Frame: Date when baseline EPIC-26 completed to 6 months post radiation therapy, 1 year post radiation therapy and 5 years post radiation therapy. ]
  • Fatigue status as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue-domain change score [ Time Frame: From the date when the baseline PROMIS is completed to the last week of treatment. ]
  • Assessment and comparison of Quality Adjusted Life Years (QALYs) [ Time Frame: From the baseline QALYs assessment to the last week of radiation therapy (RT), 3 months post RT, 6 months post RT, 1 year post RT and 5 years post RT. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2011)
  • Cause-specific survival of these
  • Distant metastasis-free survival of these patients
  • Biochemical failure by the Phoenix definition (PSA ≥ 2 ng/mL over the nadir PSA
  • Incidence of "acute" adverse events as assessed by CTCAE current version
  • Time to "late" grade 3+ adverse events as assessed by CTCAE current version
  • Prostate cancer-specific HRQOL change as measured by the EPIC-26 (bowel or urinary domain)
  • Fatigue status as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue-domain change score
  • Assessment and comparison of Quality Adjusted Life Years (QALYs)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer
Official Title  ICMJE Androgen Deprivation Therapy and High Dose Radiotherapy With or Without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial
Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells.

PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.

Detailed Description

OBJECTIVES:

Primary

  • Demonstrate that prophylactic, neoadjuvant, androgen-deprivation therapy (NADT) and whole-pelvic radiation therapy (WPRT) will result in improvement in overall survival (OS) of patients with "unfavorable" intermediate-risk or "favorable" high-risk prostate cancer compared to NADT and high-dose prostate (P) and seminal vesicle (SV) radiation therapy (RT) using intensity-modulated RT (IMRT) or external-beam RT (EBRT) with a high-dose rate (HDR) or a permanent prostate (radioactive seed) implant (PPI) boost.

Secondary

  • Demonstrate that prophylactic WPRT improves biochemical control.
  • Determine the distant metastasis (DM)-free survival.
  • Determine the cause-specific survival (CSS).
  • Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT, P, and SV RT.
  • Determine whether health-related quality of life (HRQOL), as measured by the Expanded Prostate Cancer Index Composite (EPIC), significantly worsens with increasing aggressiveness of treatment (i.e., Arm 2, NADT + WPRT).
  • Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (PROMIS Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (IL-1, IL-1ra, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein).
  • Demonstrate an incremental gain in OS and CSS with more aggressive therapy that outweighs any detriments in the primary generic domains of HRQOL (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).
  • Determine whether changes in fatigue from baseline to the next three time points (week prior to RT, last week of treatment, and 3 months after treatment) are associated with changes in circulating cytokines, mood, sleep, and daily activities across the same time points.
  • Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses.

OUTLINE: This is a multicenter study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiotherapy boost (IMRT vs brachytherapy [Low-dose rate (LDR) using PPI or HDR]), and duration of androgen-deprivation therapy (short-term [6 months] vs long-term [32 months]). Patients are randomized to 1 of 2 treatment arms.

All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily or flutamide PO thrice daily for 6 months, and luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy comprising leuprolide acetate, goserelin acetate, buserelin, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) every 1 to 3 months beginning 2 months prior to radiotherapy and continuing for 6 or 32 months.

Radiotherapy begins within 8 weeks after beginning LHRH agonist/antagonist injection.

  • Arm I: Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (iodine I 125 or palladium Pd 103 may be used as the radioisotope).
  • Arm II: Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.

NOTE: * Patients undergoing brachytherapy implant receive 5 weeks of IMRT, 3D-CRT, or WPRT.

Patients may undergo blood and urine sample collection for correlative studies. Primary tumor tissue samples may also be collected.

Patients may complete the Expanded Prostate Cancer Index Composite (EPIC), the PROMIS-Fatigue Short Form, and the EuroQol (EQ-5D) quality-of-life (QOL) questionnaires at baseline and periodically during treatment. Patients who participate in the QOL portion of the study must also agree to periodic blood collection.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Radiation: radiation therapy
    Undergo RT using IMRT or 3D-CRT
  • Radiation: Whole-pelvic radiotherapy (WPRT)
    Undergo whole-pelvic radiotherapy (WPRT)
Study Arms  ICMJE
  • Active Comparator: Arm I
    Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (I 125 or Pd 103 may be used as the radioisotope).
    Intervention: Radiation: radiation therapy
  • Experimental: Arm II
    Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.
    Intervention: Radiation: Whole-pelvic radiotherapy (WPRT)
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: June 24, 2019)
2592
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2011)
2580
Estimated Study Completion Date  ICMJE July 2031
Estimated Primary Completion Date July 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations:

    • Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50 ng/mL (includes intermediate- and high-risk patients)
    • Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR
    • Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml
    • Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL Patients previously diagnosed with low risk prostate cancer undergoing active surveillance who are re-biopsied and found to have unfavorable intermediate risk disease or favorable high risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure.
  • History and/or physical examination (to include at a minimum digital rectal examination of the prostate and examination of the skeletal system and abdomen) within 90 days prior to registration
  • Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT or MR), (but not by nodal sampling, or dissection) within 90 days prior to registration

    • Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.5 cm
    • Patients status post a negative lymph node dissection are not eligible
  • No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (Na F PET/CT is an acceptable substitute)

    • Equivocal bone scan findings are allowed if plain films (or CT or MRI) are negative for metastasis
  • Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 120 days prior to registration
  • Study entry PSA should not be obtained during the following time frames:

    • Ten-day period following prostate biopsy
    • Following initiation of hormonal therapy
    • Within 30 days after discontinuation of finasteride
    • Within 90 days after discontinuation of dutasteride

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
  • No prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years (1,095 days) and not in the pelvis

    • E.g., carcinoma in situ of the oral cavity is permissible; however, patients with prior history of bladder cancer are not allowed
    • No prior hematological (e.g., leukemia, lymphoma, or myeloma) malignancy
    • No previous radical surgery (prostatectomy) or cryosurgery for prostate cancer
    • No previous pelvic irradiation, prostate brachytherapy or bilateral orchiectomy
    • No previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., DES), or surgical castration (orchiectomy)
  • Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both LHRH agonist and oral anti-androgen) is ≤ 45 days prior to the date of registration.
  • No severe, active co-morbidity, defined as any of the following:

    • 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 registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects or severe liver dysfunction
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition

      • Protocol-specific requirements may also exclude immuno-compromised patients
      • HIV testing is not required for entry into this protocol
  • No patients who are sexually active and not willing/able to use medically acceptable forms of contraception
  • No prior allergic reaction to the hormones involved in this protocol

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radical surgery (prostatectomy) or cryosurgery for prostate cancer
  • No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
  • No prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g., degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol (DES) ), or surgical castration (orchiectomy)
  • No prior pharmacologic androgen ablation for prostate cancer unless the onset of androgen ablation is ≤ 45 days prior to the date of registration
  • No finasteride within 30 days prior to registration
  • No dutasteride or dutasteride/tamsulosin (Jalyn) within 90 days prior to registration
  • No prior or concurrent cytotoxic chemotherapy for prostate cancer

    • Prior chemotherapy for a different cancer is allowable
  • No prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy fields
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 Canada,   Hong Kong,   Israel,   Singapore,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01368588
Other Study ID Numbers  ICMJE RTOG-0924
CDR0000701128
NCI-2011-02674 ( Registry Identifier: Clinical Trials Reporting Program (CTRP) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Radiation Therapy Oncology Group
Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • NRG Oncology
Investigators  ICMJE
Principal Investigator: Mack Roach, MD University of California, San Francisco
PRS Account Radiation Therapy Oncology Group
Verification Date June 2019

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