NCT01546987已完成3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 239
- 试验地点
- 334
- 主要终点
- Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)
研究概览
简要总结
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.
详细描述
OBJECTIVES:
Primary
- 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).
Secondary
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
- •History/physical examination within 60 days prior to registration.
- •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.
- •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.
- •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.
- •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.
- •Prior testosterone administration is allowed if last administered at least 90 days prior to registration.
- •Zubrod Performance Status 0-1 within 21 days prior to registration
- •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.)
- •Serum creatinine < 2.0 mg/dl and creatinine clearance (can be calculated) > 40 mL/minute within 21 days prior to registration
- •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
- •Serum testosterone within 21 days prior to registration
- •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
- •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
- •Screening calculated ejection fraction of ≥ to institutional lower limit of normal by multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO).
- •Baseline electrocardiogram (ECG) within 180 days prior to registration
- •Patients, even if surgically sterilized (ie, status post vasectomy), who:
- •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
- •Agree to completely abstain from intercourse.
- •Patient must be able to provide study-specific informed consent prior to study entry.
排除标准
- •Definite evidence of metastatic disease.
- •Pathologically positive lymph nodes or nodes > 2.0 cm on imaging.
- •Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason.
- •Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.
- •Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).
- •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).
- •Previous hormonal therapy for > 50 days.
- •Known hypersensitivity to TAK-700 or related compounds
- •A history of adrenal insufficiency
- •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.
- •New York Heart Association Class III or IV heart failure.
- •ECG abnormalities of:
- •Q-wave infarction, unless identified 6 or more months prior to screening
- •QTc interval > 460 msec
- •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.
- •Prior allergic reaction to the drugs involved in this protocol.
- •Study entry PSA obtained during the following time frames:
- •10-day period following prostate biopsy;
- •following initiation of hormonal therapy.
- •Cushing's syndrome
- •Severe chronic renal disease (serum creatinine > 2.0 mg/dl and confirmed by creatinine clearance < 40 mL/minute)
- •Chronic liver disease (bilirubin > 1.5x ULN, ALT or AST > 2.5x ULN)
- •Chronic treatment with glucocorticoids within one year
- •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)
- •Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.
- •Major surgery within 14 days prior to registration
- •Serious infection within 14 days prior to registration
- •Uncontrolled nausea, vomiting, or diarrhea [Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3] despite appropriate medical therapy at the time of registration
- •Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets
研究组 & 干预措施
ADT + RT
Active Comparator
Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
干预措施: GnRH agonist (Drug)
ADT + RT
Active Comparator
Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
干预措施: Anti-androgen (Drug)
ADT + RT
Active Comparator
Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
干预措施: Radiation therapy (Radiation)
TAK-700 + ADT + RT
Experimental
TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
干预措施: GnRH agonist (Drug)
TAK-700 + ADT + RT
Experimental
TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
干预措施: Anti-androgen (Drug)
TAK-700 + ADT + RT
Experimental
TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
干预措施: TAK-700 (Drug)
TAK-700 + ADT + RT
Experimental
TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)
时间窗: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.
Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from secondary (original protocol) to primary. Biochemical failure will be defined by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or the initiation of salvage androgen deprivation therapy. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.
次要结局
- Serum High-density Lipoprotein (HDL)(Baseline, 12 months, 24 months)
- Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol)(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Serum Testosterone(Baseline,12 months, 24 months)
- Fasting Total Cholesterol(Baseline, 12 months, 24 months)
- Fasting Plasma Glucose(Baseline, 12 months, 24 months)
- Fasting Plasma Insulin(Baseline, 12 months, 24 months)
- Percentage of Participants With Grade 3 or Higher Adverse Events(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year(Baseline, one year)
- Change From Baseline in Body Mass Index (BMI)(Baseline and yearly to five years.)
- Percentage of Participants With Local Progression(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates reported.)
- Percentage of Participants With Distant Metastases(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Percentage of Participants With General Clinical Treatment Failure(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Percentage of Participants With Death Due to Prostate Cancer(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Number of Patients With Clinical Survivorship Events(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year(Baseline, one year)
- Serum High-density Lipoprotein (LDL)(Baseline, 12 months, 24 months)
- Hemoglobin A1c(Baseline, 12 months, 24 months)
- Number of Participants by Highest Grade Adverse Event(From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
- Testosterone Recovery at 12 and 24 Months(From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years.)
- Median Testosterone Recovery Time(From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.)
研究者
研究点 (334)
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