Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: bicalutamide; flutamide; LHRH agonist (antagonist) therapy; Dose-Escalated Radiation Therapy
Intervention description: Administered orally at a dose of one 50 mg tablet per day, beginning within (before, same day as, or after) 10 days of the date of the first LHRH agonist (antagonist) therapy administration and continuing for a total duration of 6 months.; Administered orally at a dose of 250 mg (two 125-mg capsules) three times a day for a total daily dose of 750 mg, beginning within (before, same day as, or after) 10 days of with the date of the first LHRH agonist (antagonist) therapy administration and continuing for a total duration of 6 months.; LHRH agonist (antagonist) therapy consists of leuprolide, goserelin, buserelin, triptorelin, or degarelix. The manufacturer's instructions should be followed. The first administration occurs with the start of anti-androgen treatment 8 weeks prior to the start of RT. The total duration of LHRH agonist (antagonist) therapy is 6 months.; External beam radiotherapy (EBRT) as 3D Conformal Radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT). Brachytherapy is optional, at the discretion of the treating physician. Patients treated entirely via EBRT receive 79.2 Gy delivered in 1.8 Gy fractions. Patients who receive brachytherapy as a component of their RT receive 45 Gy EBRT in 1.8 Gy fractions. Low-dose brachytherapy boost occurs following the EBRT portion of treatment no more than 4 weeks following its completion.High-dose rate brachytherapy boost is delivered in 2 fractions separated by a minimum time span of 6 hours and the implant(s) may be performed during the EBRT portion of the treatment or within 1 week prior to its initiation or following its completion.
Intervention MeSH terms: Leuprolide; Goserelin; Triptorelin Pamoate; Flutamide; Bicalutamide; Buserelin; Androgens; Androgen Antagonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1538.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill
      tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells.
      Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not
      yet known whether radiation therapy is more effective with or without androgen-deprivation
      therapy in treating patients with prostate cancer.

      PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it
      works compared with radiation therapy given together with androgen-deprivation therapy in
      treating patients with prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma, at
             intermediate risk for recurrence, within 180 days prior to registration as determined
             by having one or more of the following intermediate-risk features: Gleason score 7;
             prostate-specific antigen (PSA) >10 but ≤20; clinical stage T2b-T2c.

               -  Patients previously diagnosed with low risk (Gleason score ≤ 6, clinical stage <
                  T2a, and PSA < 10) prostate cancer undergoing active surveillance who are
                  re-biopsied and found to have intermediate risk disease according to the protocol
                  criteria are eligible for enrollment within 180 days of the repeat biopsy
                  procedure.

          2. Clinically negative lymph nodes as established by imaging (pelvic +/- abdominal CT or
             MRI), nodal sampling, or dissection within 60 days prior to registration, except as
             noted immediately below:

               -  Patients with a single intermediate risk factor only do not require
                  abdominopelvic imaging, but these studies may be obtained at the discretion of
                  the treating physician. Patients with 2 or 3 risk factors are required to undergo
                  pelvic +/- abdominal CT or MRI.

               -  Patients with lymph nodes equivocal or questionable by imaging are eligible
                  without biopsy if the nodes are ≤1.5 cm; any node larger than this on imaging
                  will require negative biopsy for eligibility.

          3. No evidence of bone metastases (M0) on bone scan within 60 days prior to registration.

               -  Bone scan is not required for patients enrolled with a single intermediate risk
                  factor only, but this scan may be obtained at the discretion of the treating
                  physician. Patients with 2 or 3 risk factors will require a negative bone scan
                  for eligibility.

               -  Equivocal bone scan findings are allowed if plain film x-rays are negative for
                  metastasis.

          4. History/physical examination (to include, at a minimum, digital rectal examination of
             the prostate and examination of the skeletal system and abdomen, and formal
             comorbidity assessment via the ACE-27 instrument) within 60 days prior to
             registration.

          5. Zubrod Performance Status 0-1

          6. Age ≥ 18

          7. Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott,
             Hybritech) within 60 days prior to registration

               -  Study entry PSA must not be obtained during the following time frames: (1) 10-day
                  period following prostate biopsy; (2) following initiation of ADT; (3) within 30
                  days after discontinuation of finasteride; or (4) within 90 days after
                  discontinuation of dutasteride.

          8. For patients undergoing brachytherapy only: complete blood count (CBC)/differential
             obtained within 60 days prior to registration, with adequate bone marrow function
             defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention
                  to achieve Hgb ≥ 8.0 g/dl is acceptable.)

          9. Patient must be able to provide study-specific informed consent prior to study entry.

        Exclusion Criteria:

          1. Patients with Gleason Score ≥ 8; PSA > 20; OR Clinical Stage ≥ T3 are ineligible for
             this trial.

               -  Should findings of extracapsular extension or seminal vesicle invasion be noted
                  on prostate MRI, this study, if used, will not render patients ineligible for
                  accrual to this protocol. Primary tumor staging for eligibility purposes is to be
                  based on palpable or core biopsy evidence only with respect to extracapsular
                  extension or seminal vesicle involvement.

          2. Patients with all three intermediate risk factors who also have ≥ 50% of the number of
             their biopsy cores positive for cancer are ineligible for this trial.

          3. Prior invasive malignancy (except non-melanomatous skin cancer) or hematological
             (e.g., leukemia, lymphoma, myeloma) malignancy unless disease free for a minimum of 5
             years (prior diagnoses of carcinoma in situ are permitted)

          4. Prior radical surgery (prostatectomy), high-intensity focused ultrasound (HIFU) or
             cryosurgery for prostate cancer

          5. Prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide),
             antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral
             orchiectomy

          6. Use of finasteride within 30 days prior to registration

          7. Use of dutasteride within 90 days prior to registration

          8. Prior or concurrent cytotoxic chemotherapy for prostate cancer; prior chemotherapy for
             a different cancer is permitted.

          9. Prior RT, including brachytherapy, to the region of the study cancer that would result
             in overlap of RT fields

               -  Any patient undergoing brachytherapy must have transrectal ultrasound
                  confirmation of prostate volume <60 cc, American Urological Association Symptom
                  Index (AUA-SI) score ≤15 within 60 days of registration, and no history of prior
                  transurethral resection of the prostate (TURP); prior TURP is permitted for
                  patients who receive EBRT only)

         10. 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 registration

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days before
                  registration

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
                  Control and Prevention (CDC) definition; note, however, that HIV testing is not
                  required for entry into this protocol. While the treatment employed in this study
                  is not significantly immunosuppressive, it is felt that a diagnosis of AIDS
                  associated with prostate cancer is likely to impact this study's primary endpoint
                  of overall survival. Patients who are HIV seropositive but do not meet criteria
                  for diagnosis of AIDS are eligible for study participation.

         11. Men who are sexually active with a woman of child-bearing potential and not
             willing/able to use medically acceptable forms of contraception (e.g., surgical,
             barrier, medicinal) during protocol treatment and during the first 3 months after
             cessation of protocol treatment; this exclusion is necessary because the treatment
             involved in this study may be significantly teratogenic.