Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: GnRH agonist; Anti-androgen; TAK-700; Radiation therapy
Intervention description: LHRH agonists are administered with a variety of techniques. The manufacturer's instructions should be followed. Begins within 6 weeks after registration (if not started prior) at same time as anti-androgen and TAK-700 (if applicable).; Starts at same time as GnRH agonist, ends at end of radiation therapy. Either flutamide (orally 250 mg three times a day) or bicalutamide (orally 50 mg once a day).; 300 mg twice daily (BID) (600 mg per day) orally, continuously for 2 years starting with ADT.; Starts 8-10 weeks after initiation of ADT. Initially 45 Gy (1.8 Gy / fraction) to prostate and pelvic lymph nodes delivered with 3DCRT/IMRT, then a boost using intensity-modulated radiation therapy (IMRT), low dose rate (LDR) brachytherapy, or high dose rate (HDR) brachytherapy.
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: 239.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; stage I prostate cancer; stage IIA prostate cancer; stage IIB prostate cancer; stage III prostate cancer; stage IV prostate cancer

Summary:

      RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as steroid
      17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of
      androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells.
      This may be an effective treatment for prostate cancer when combined with hormone therapy.
      Studying quality-of-life in patients having cancer treatment may help identify the
      intermediate- and long-term effects of treatment on patients with prostate cancer.

      PURPOSE: This randomized phase III trial is studying the use of hormone therapy, including
      TAK-700, together with radiation therapy in treating patients with prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days
             prior to registration at high risk for recurrence as determined by one of the
             following combinations:

               -  Gleason Score (GS) ≥ 9, PSA ≤ 150 ng/mL, any T stage

               -  GS ≥ 8, PSA < 20 ng/mL, T stage ≥ T2

               -  GS ≥ 8, PSA ≥ 20-150 ng/mL, any T stage

               -  GS ≥ 7, PSA ≥ 20-150 ng/mL, any T stage

          2. History/physical examination within 60 days prior to registration.

          3. Clinically negative lymph nodes as established by imaging [abdominal and/or pelvic
             computerized tomography (CT) or abdominal and/or pelvic magnetic resonance imaging
             (MRI)], 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 < 2.0 cm.

          4. No distant metastases (M0) on bone scan within 90 days prior to registration (18F-Na
             bone scan is an acceptable substitute).

             •Equivocal bone scan findings are allowed if plain films are negative for metastasis.

          5. Baseline serum prostate-specific antigen (PSA) value performed with an FDA-approved
             assay (e.g., Abbott, Hybritech), obtained prior to any luteinizing hormone-releasing
             hormone (LHRH) or anti-androgen therapy, within 180 days of randomization.

          6. Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin,
             leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or
             surgical castration (orchiectomy), may have been started prior to registration,
             provided that registration is within 50 days of beginning ADT. Please note: If the
             patient has started ADT he will not be eligible to participate in the quality of life
             component of this study.

          7. Prior testosterone administration is allowed if last administered at least 90 days
             prior to registration.

          8. Zubrod Performance Status 0-1 within 21 days prior to registration

          9. Age ≥ 18

         10. Complete blood count (CBC)/differential obtained within 14 days prior to registration
             on study, with adequate bone marrow function defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥ 8.0 g/dl is acceptable.)

         11. Serum creatinine < 2.0 mg/dl and creatinine clearance (can be calculated) > 40
             mL/minute within 21 days prior to registration

         12. Bilirubin < 1.5x upper limit of normal (ULN) and alanine aminotransferase (ALT) or
             aspartate aminotransferase (AST) < 2.5x ULN within 21 days prior to registration

         13. Serum testosterone within 21 days prior to registration

         14. Chemistry (including sodium, potassium, chloride, bicarbonate (carbon dioxide), blood
             urea nitrogen (BUN), glucose, calcium, magnesium and phosphorous) and liver panels
             (including albumin and alkaline phosphatase) obtained within 21 days prior to
             registration

         15. Fasting glucose, fasting insulin, lipid panel [cholesterol, triglyceride, high-density
             lipoprotein (HDL), low-density lipoprotein (LDL)], and Hemoglobin A1C within 21 days
             prior to registration

         16. Screening calculated ejection fraction of ≥ to institutional lower limit of normal by
             multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO).

         17. Baseline electrocardiogram (ECG) within 180 days prior to registration

         18. Patients, even if surgically sterilized (ie, status post vasectomy), who:

               1. Agree to practice effective barrier contraception during the entire study
                  treatment period and for 4 months (120 days) after the last dose of study drug,
                  or

               2. Agree to completely abstain from intercourse.

         19. Patient must be able to provide study-specific informed consent prior to study entry.

        Exclusion Criteria:

          1. PSA > 150

          2. Definite evidence of metastatic disease.

          3. Pathologically positive lymph nodes or nodes > 2.0 cm on imaging.

          4. Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy
             for any reason.

          5. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not
             requiring systemic therapy for a minimum of 3 years.

          6. Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a
             different cancer is allowed).

          7. Prior radiotherapy, including brachytherapy, to the region of the prostate that would
             result in overlap of radiation therapy fields.

             •Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of
             prostate volume <60 cc, American Urological Association (AUA) 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 external beam radiation
             therapy [EBRT] only).

          8. Previous hormonal therapy for > 50 days.

          9. Known hypersensitivity to TAK-700 or related compounds

         10. A history of adrenal insufficiency

         11. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing
             arrhythmias of Grade > 2 [NCI CTCAE, version 4.02] (U.S. Department of Health and
             Human Services, National Institutes of Health National Cancer Institute, 2009),
             thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic
             cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion
             restrictive cardiomyopathy) within 6 months prior to registration. Chronic stable
             atrial fibrillation on stable anticoagulant therapy is allowed.

         12. New York Heart Association Class III or IV heart failure.

         13. ECG abnormalities of:

               1. Q-wave infarction, unless identified 6 or more months prior to screening

               2. QTc interval > 460 msec

         14. Patients who are sexually active and not willing/able to use medically acceptable
             forms of contraception; this exclusion is necessary because the treatment involved in
             this study may be significantly teratogenic.

         15. Prior allergic reaction to the drugs involved in this protocol.

         16. Study entry PSA obtained during the following time frames:

               1. 10-day period following prostate biopsy;

               2. following initiation of hormonal therapy.

         17. Cushing's syndrome

         18. Severe chronic renal disease (serum creatinine > 2.0 mg/dl and confirmed by creatinine
             clearance < 40 mL/minute)

         19. Chronic liver disease (bilirubin > 1.5x ULN, ALT or AST > 2.5x ULN)

         20. Chronic treatment with glucocorticoids within one year

         21. Uncontrolled hypertension despite appropriate medical therapy within 21 days prior to
             registration (blood pressure of greater than 150 mm Hg systolic and 90 mm Hg diastolic
             at 2 separate measurements no more than 60 minutes apart during Screening visit)

         22. Unwilling or unable to comply with the protocol or cooperate fully with the
             investigator and site personnel.

         23. Major surgery within 14 days prior to registration

         24. Serious infection within 14 days prior to registration

         25. Uncontrolled nausea, vomiting, or diarrhea [Common Terminology Criteria for Adverse
             Events (CTCAE) grade ≥ 3] despite appropriate medical therapy at the time of
             registration

         26. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of TAK-700, including difficulty swallowing tablets