Clinical Trials (PDQ®)
|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 Lead Organizations/Sponsors
Radiation Therapy Oncology GroupNational Cancer Institute
|M. Dror Michaelson||Principal Investigator|
|University of Michigan Comprehensive Cancer Center|
|Daniel A Hamstra||Ph: 734-936-4300|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01546987
ClinicalTrials.gov processed this data on November 12, 2014
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