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
- To evaluate the difference in overall survival of patients with clinically localized
prostate cancer with unfavorable prognostic features between a) standard treatment
(androgen-deprivation therapy [ADT] + radiotherapy) and b) standard treatment with the
addition of 24 months of steroid 17alpha-monooxygenase TAK-700 (TAK-700).
- To characterize differences between the treatment groups with respect to incidence of
unexpected grade ≥ 3 adverse events and/or clinically significant decrement in
patient-reported quality of life (QOL) among subjects treated with TAK-700.
- To compare rates and cumulative incidence of biochemical control (freedom from PSA
failure), local/regional progression, and distant metastases.
- To compare rate and cumulative incidence of clinical failure, defined as
prostate-specific antigen (PSA) > 25 ng/mL, documented local disease progression,
regional or distant metastasis, or initiation of ADT.
- To compare prostate cancer-specific survival and other-cause mortality.
- To compare the change in severity of fatigue as measured by the Patient-Reported
Outcome Measurement Information System (PROMIS) fatigue short form.
- To compare changes in patient-reported QOL as measured by Expanded Prostate Cancer
Index Composite (EPIC).
- To assess quality-adjusted survival using the EQ-5D.
- To compare nadir and average serum testosterone at 12 and 24 months during treatment.
- To compare changes in hemoglobin A1C, fasting glucose, and fasting insulin during 24
months of systemic treatment and during the first three years of follow-up.
- To compare changes in fasting lipid levels during 24 months of treatment and during the
first three years of follow-up.
- To compare changes in body mass index (BMI) during 24 months of treatment and during
the first three years of follow-up.
- To compare the incidence of adverse events ascertained via CTCAE version 4.
- To compare the rate of recovery of testosterone to > 230 ng/dL (accepted threshold for
supplementation) after 12 and 24 months of follow-up.
- To compare the median time to recovery of testosterone to > 230 ng/dL during the first
five years of follow-up.
- To assess cumulative incidence of relevant clinical survivorship endpoints including
new diagnosis of type 2 diabetes, coronary artery disease, myocardial infarction,
stroke, pulmonary embolism, deep vein thrombosis, or osteoporotic fracture.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to risk
group (see Disease Characteristics) and type of radiation therapy (RT) boost
(intensity-modulated RT [IMRT] vs brachytherapy). Patients are randomized to 1 of 2
- Arm I: Patients receive standard androgen suppression (AS) with a luteinizing
hormone-releasing hormone (LHRH) agonist (such as leuprolide, goserelin, buserelin, or
triptorelin) for 24 months from initiation and oral (PO) antiandrogen (such as
flutamide or bicalutamide) beginning 2 months prior and for the duration of radiation
- Arm II: Patients receive the same standard AS with LHRH agonist and oral antiandrogen
as in arm 1. Patients also receive steroid 17alpha-monooxygenase TAK-700 (TAK-700) PO
twice daily (BID) for 2 years.
In both arms, patients undergo IMRT or 3D-conformal RT to the whole pelvis once daily, 5
days a week, for 6-8 weeks. Some patients also receive brachytherapy.
Quality of life is assessed via the Patient-Reported Outcome Measurement Information System
(PROMIS) Fatigue Scale, the Expanded Prostate Cancer Index Composite (EPIC-26), and the
EuroQol (EQ-5D) assessments at baseline and periodically during the study.
Serum may be collected from some patients for correlative studies.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6
months for 1 year, and then annually thereafter.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
M. Dror Michaelson, MD, PhD
Massachusetts General Hospital
|Natalie Warren Bryant Cancer Center at St. Francis Hospital||Tulsa, Oklahoma 74136|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|Maine Center for Cancer Medicine and Blood Disorders - Scarborough||Scarborough, Maine 04074|
|St. Vincent Hospital Regional Cancer Center||Green Bay, Wisconsin 54307-3508|
|St. Mary's Hospital Medical Center - Green Bay||Green Bay, Wisconsin 54303|
|Bay Area Cancer Care Center at Bay Area Medical Center||Marinette, Wisconsin 54143|
|David C. Pratt Cancer Center at St. John's Mercy||St. Louis, Missouri 63141|
|Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center||Los Angeles, California 90048-1865|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Gundersen Lutheran Center for Cancer and Blood||La Crosse, Wisconsin 54601|
|All Saints Cancer Center at Wheaton Franciscan Healthcare||Racine, Wisconsin 53405|
|Delaware County Regional Cancer Center at Delaware County Memorial Hospital||Drexel Hill, Pennsylvania 19026|
|Missouri Baptist Cancer Center||St. Louis, Missouri 63131|
|York Cancer Center at Apple Hill Medical Center||York, Pennsylvania 17405|
|Jon and Karen Huntsman Cancer Center at Intermountain Medical Center||Murray, Utah 84157|
|Radiological Associates of Sacramento Medical Group, Incorporated||Sacramento, California 95815|
|Gibbs Regional Cancer Center at Spartanburg Regional Medical Center||Spartanburg, South Carolina 29303|
|Solano Radiation Oncology Center||Vacaville, California 95687|
|Auburn Radiation Oncology||Auburn, California 95603|
|Radiation Oncology Centers - Cameron Park||Cameron Park, California 95682|
|Radiation Oncology Center - Roseville||Roseville, California 95661|
|Mercy Cancer Center at Mercy San Juan Medical Center||Carmichael, California 95608|
|St. Agnes Hospital Cancer Center||Baltimore, Maryland 21229|
|Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital||Fort Worth, Texas 76104|
|Adams Cancer Center||Gettysburg, Pennsylvania 17325|
|Cherry Tree Cancer Center||Hanover, Pennsylvania 17331|