Clinical Trials /

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

NCT01368588

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: RTOG-0924
  • SECONDARY ID: CDR0000701128
  • SECONDARY ID: NCI-2011-02674
  • NCT ID: NCT01368588
  • NCT ALIAS: NCT02673190

Conditions

  • Prostate Cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm IActive ComparatorPatients 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).
    Arm IIExperimentalPatients 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.

      Eligibility Criteria

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

      Primary Outcome Measures

      Measure:Overall Survival
      Time Frame:From date of randomization to the date of death.
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Cause-specific survival
      Time Frame:From date of randomization to the date of death due to prostate cancer.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:
      Measure: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.
      Safety Issue:
      Description:

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Radiation Therapy Oncology Group

      Trial Keywords

      • adenocarcinoma of the prostate
      • stage I prostate cancer
      • stage IIA prostate cancer
      • stage IIB prostate cancer
      • stage III prostate cancer

      Last Updated

      May 18, 2017