RTOG 1115 Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT)with a GnRH Agonist vs. Dose Escalated Radiation Therapy and Enhanced ADT with a GnRH Agonist and TAK-700 for Men with High Risk Prostate Cancer

Summary

Though standard aDT with a GnRH agonist has clearly been shown to improve the efficacy of radiation therapy, no trial has yet built upon this foundation with the use of more profound androgen deprivation in this clinical setting. this study proposes to examine the combination of radiation with enhanced aDT using a GnRH agonist and TaK-700. This combination of hormonal agents has been shown to suppress serum testosterone to undetectable levels. There are two arms. arm 2 differs from arm 1 in that arm 2 includes the addition of TaK-700:
arm 1: androgen Deprivation Therapy (GnRH agonist for 24 months with concurrent oral antiandrogen until completion of radiation) + Dose escalated Radiation to start 8-10 weeks after initiation of aDT. (initially, 45 Gy to prostate and pelvic lymph nodes delivered with 3DCRT/iMRT with a boost to be provided with iMRT, LDR implant, or HDR implant.)
arm 2: androgen Deprivation Therapy (GnRH agonist for 24 months with concurrent oral antiandrogen until completion of radiation) + TaK-700 twice daily for 24 months + Dose escalated Radiation (to start 8-10 weeks after initiation of aDT. initially, 45 Gy to prostate and pelvic lymph nodes delivered with 3DCRT/iMRT with a boost to be provided with iMRT, LDR implant, or HDR implant.)

For patients on either arm 1 or arm 2, who began aDT prior to enrollment, if prior treatment was with LHRH agonist alone, an oral anti-androgen (plus or minu TaK-700) should be added at the time of enrollment.

Participant Eligibility

3.1.1 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 > 9, PSA <150, T-Stage Any
Gleason score 8, PSA <20, T-Stage >T2
Gleason score 8, PSA > 20-150, T-Stage Any
Gleason score 7, PSA > 20 x 150, T-Stage Any
3.1.2 History/physical examination within 60 days prior to registration.
3.1.3 Clinically negative lymph nodes as established by imaging (abdominal and/or pelvic CT or
abdominal and/or pelvic MRI), nodal sampling, or dissection within 90 days prior to registration.
3.1.3.1 Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are
< 2.0 cm.
3.1.4 No distant metastases (M0) on bone scan within 90 days prior to registration.
3.1.4.1 Equivocal bone scan findings are allowed if plain films are negative for metastasis.
3.1.5 Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech),
obtained prior to any LHRH or antiandrogen therapy, within 180 days of randomization.
3.1.6 Prior testosterone administration is allowed if last administered at least 90 days prior to
registration.
3.1.7 Height, weight, Zubrod Performance Status 0-1 within 21 days prior to registration
3.1.8 Age >= 18
3.1.9 CBC/differential obtained within 14 days prior to registration on study, with adequate bone
marrow function defined as follows:
3.1.9.1 Absolute neutrophil count (ANC) >= 1,800 cells/mm3
3.1.9.2 Platelets >= 100,000 cells/mm3
3.1.9.3 Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
8.0 g/dl is acceptable.)
3.1.10 Serum creatinine < 2.0 mg/dl and creatinine clearance > 40 mL/minute within 21 days prior to registration
3.1.11 Bilirubin < 1.5x ULN and ALT or AST < 2.5x ULN within 21 days prior to registration
3.1.12 Screening calculated ejection fraction of >= to institutional lower limit of normal by multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO).
3.1.13 Baseline ECG within 180 days prior to registration
3.1.14 Patients, even if surgically sterilized (ie, status post vasectomy), who:
(a) 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
(b) Agree to completely abstain from intercourse.
3.1.15 Patient must be able to provide study-specific informed consent prior to study entry.