Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Supportive care, Treatment||Closed||18 and over||NCI, Other||RTOG 1115|
CDR0000727326, NCI-2012-00700, NCT01546987
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.
Further Study Information
- 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 treatment arms.
- 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 therapy (RT).
- 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.
- 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 (risk group):
- 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
- Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech), obtained prior to any luteinizing hormone-releasing hormone (LHRH) agonist or antiandrogen therapy, within 180 days of randomization
- Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin, leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., diethyl- stilbestrol [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
- 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
- Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 2.0 cm
- No distant metastases (M0) on bone scan within 90 days prior to registration
- Equivocal bone scan findings are allowed if plain films are negative for metastasis
- No definite evidence of metastatic disease
- 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 radiotherapy (EBRT) only
- Height, weight, Zubrod performance status 0-1
- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm^3
- Platelets ≥ 100,000 cells/mm^3
- Hemoglobin ≥ 8.0 g/dL (The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
- Serum creatinine < 2.0 mg/dL
- Creatinine clearance > 40 mL/minute
- Bilirubin < 1.5 x upper limit of normal (ULN)
- Alanine aminotranserase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN
- No PSA > 150 ng/mL
- Screening calculated ejection fraction ≥ ULN by multiple-gated acquisition (MUGA) scan or by echocardiogram
- 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.
- Patients, even if surgically sterilized (i.e., status post vasectomy), must 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
- No prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years
- No known hypersensitivity to TAK-700 or related compounds
- No history of adrenal insufficiency
- No history of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade > 2 (NCI CTCAE, version 4.02) thromboembolic events (e.g., 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
- No New York Heart Association Class III or IV heart failure
- No ECG abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening, or corrected QT (QTc) interval > 460 msec
- No prior allergic reaction to the drugs involved in this protocol
- No Cushing syndrome
- No severe chronic renal disease or chronic liver disease
- No 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)
- No serious infection within 14 days prior to registration
- No uncontrolled nausea, vomiting, or diarrhea (CTCAE grade ≥ 3) despite appropriate medical therapy at the time of registration
- No known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior testosterone administration is allowed if last administered at least 90 days prior to registration
- No prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason
- No prior systemic chemotherapy for prostate cancer
- Prior chemotherapy for a different cancer is allowed
- No prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields
- No previous hormonal therapy for > 50 days
- No chronic treatment with glucocorticoids within one year
- No major surgery within 14 days prior to registration
- No other investigational agent
- No other anticancer therapy
- No concurrent hormonal therapies including estrogens or herbal products
- No concurrent ketoconazole or aminoglutethimide
- No chronic use of systemic corticosteroids, such as oral prednisone
Trial Contact Information
Trial Lead Organizations/Sponsors
Radiation Therapy Oncology Group
- National Cancer Institute
- NRG Oncology
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01546987
ClinicalTrials.gov processed this data on May 11, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.