Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage IIA prostate cancer, stage IIB prostate cancer, stage III prostate cancer, stage IV prostate cancer
Brief summary
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.
Detailed description
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. 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. After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.
Interventions
DRUGGnRH agonist
LHRH agonists are administered with a variety of techniques. The manufacturer's instructions should be followed. Begins within 6 weeks after registration (if not started prior) at same time as anti-androgen and TAK-700 (if applicable).
DRUGAnti-androgen
Starts at same time as GnRH agonist, ends at end of radiation therapy. Either flutamide (orally 250 mg three times a day) or bicalutamide (orally 50 mg once a day).
DRUGTAK-700
300 mg twice daily (BID) (600 mg per day) orally, continuously for 2 years starting with ADT.
RADIATIONRadiation therapy
Starts 8-10 weeks after initiation of ADT. Initially 45 Gy (1.8 Gy / fraction) to prostate and pelvic lymph nodes delivered with 3DCRT/IMRT, then a boost using intensity-modulated radiation therapy (IMRT), low dose rate (LDR) brachytherapy, or high dose rate (HDR) brachytherapy.
Sponsors
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 (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 2. History/physical examination within 60 days prior to registration. 3. 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. 4. 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. 5. 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. 6. 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. 7. Prior testosterone administration is allowed if last administered at least 90 days prior to registration. 8. Zubrod Performance Status 0-1 within 21 days prior to registration 9. Age ≥ 18 10. 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.) 11. Serum creatinine \< 2.0 mg/dl and creatinine clearance (can be calculated) \> 40 mL/minute within 21 days prior to registration 12. 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 13. Serum testosterone within 21 days prior to registration 14. 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 15. 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 16. Screening calculated ejection fraction of ≥ to institutional lower limit of normal by multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO). 17. Baseline electrocardiogram (ECG) within 180 days prior to registration 18. Patients, even if surgically sterilized (ie, status post vasectomy), who: 1. 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 2. Agree to completely abstain from intercourse. 19. Patient must be able to provide study-specific informed consent prior to study entry.
Exclusion criteria
1. PSA \> 150 2. Definite evidence of metastatic disease. 3. Pathologically positive lymph nodes or nodes \> 2.0 cm on imaging. 4. Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason. 5. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years. 6. Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed). 7. 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). 8. Previous hormonal therapy for \> 50 days. 9. Known hypersensitivity to TAK-700 or related compounds 10. A history of adrenal insufficiency 11. 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. 12. New York Heart Association Class III or IV heart failure. 13. ECG abnormalities of: 1. Q-wave infarction, unless identified 6 or more months prior to screening 2. QTc interval \> 460 msec 14. 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. 15. Prior allergic reaction to the drugs involved in this protocol. 16. Study entry PSA obtained during the following time frames: 1. 10-day period following prostate biopsy; 2. following initiation of hormonal therapy. 17. Cushing's syndrome 18. Severe chronic renal disease (serum creatinine \> 2.0 mg/dl and confirmed by creatinine clearance \< 40 mL/minute) 19. Chronic liver disease (bilirubin \> 1.5x ULN, ALT or AST \> 2.5x ULN) 20. Chronic treatment with glucocorticoids within one year 21. 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) 22. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel. 23. Major surgery within 14 days prior to registration 24. Serious infection within 14 days prior to registration 25. Uncontrolled nausea, vomiting, or diarrhea \[Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3\] despite appropriate medical therapy at the time of registration 26. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum High-density Lipoprotein (LDL) | Baseline, 12 months, 24 months | — |
| Hemoglobin A1c | Baseline, 12 months, 24 months | — |
| Fasting Plasma Glucose | Baseline, 12 months, 24 months | — |
| Fasting Plasma Insulin | Baseline, 12 months, 24 months | — |
| Change From Baseline in Body Mass Index (BMI) | Baseline and yearly to five years. | Body Mass Index (BMI) is a person's weight in kilograms (or pounds) divided by the square of height in meters (or feet). Change from baseline = time point value - baseline value. |
| Serum Testosterone | Baseline,12 months, 24 months | — |
| Fasting Total Cholesterol | 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. | Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from primary (original protocol) to secondary. Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided. |
| 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. | Time to grade 3 or higher adverse event (event) is defined as time from randomization to the date of first event, last known follow-up (censored), or death without failure (competing risk). Event 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. |
| 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. | Local recurrence (failure) is defined as biopsy proven recurrence within the prostate gland. Time to failure is defined as time from randomization to the date of 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. |
| 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. | Distant metastases (failure) is defined as imaging or biopsy demonstrated evidence for systemic recurrence. Biopsy was not required, however it was encouraged in absence of a rising PSA. 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. Note, the protocol lists this endpoint as regional or distant metastasis, but regional progression data was not collected. |
| 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. | General clinical treatment failure (GCTF) is defined as: PSA \> 25 ng/ml, documented local disease progression, regional or distant metastasis, or initiation of salvage androgen deprivation therapy. Failure time is defined as time from registration to the date of 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. |
| 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. | Time to prostate cancer death is defined as time from randomization to the date of death due to prostate cancer, last known follow-up (censored), or death due to other causes (competing risk). Failure rates were to be estimated using the cumulative incidence method. If too few events occur for meaningful estimates, then only counts of events will be reported. |
| Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year | Baseline, one year | The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year. |
| Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Baseline, one year | The EPIC-Short Form is a 26-item, validated self-administered tool to assess disease-specific aspects of prostate cancer and its therapies consisting of five summary domains (bowel, urinary incontinence, urinary irritation/obstruction, sexual, and hormonal function). Responses for each item form a Likert scale which are transformed to a 0-100 scale. A domain score is the average of the transformed domain item scores, ranging from 0-100 with higher scores representing better health-related quality of life (HRQOL). Change at one year is defined as one-year value - baseline value. Positive change at one year indicates improved quality of life. |
| 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. | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data |
| 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. | Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Time to testosterone recovery is defined as time from randomization to the date of testosterone recovery, biochemical, local, or distant failure (competing risk), salvage therapy (competing risk), death (competing risk), or last known follow-up (censored). Testosterone recovery rates are estimated using the cumulative incidence method. |
| 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. | Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Testosterone recovery rates are estimated using the Kaplan-Meier method, censoring for biochemical, local, or distant failure, salvage therapy, death, and otherwise alive without event. Testosterone recovery time is defined as time from randomization to testosterone recovery or censoring. |
| Serum High-density Lipoprotein (HDL) | Baseline, 12 months, 24 months | — |
| 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. | Clinical survivorship events are defined as the following newly diagnosed non-fatal cardiovascular events or other clinical endpoints relevant to prostate cancer survivorship: type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and osteoporotic fracture. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORM. Dror Michaelson, MD, PhD
Massachusetts General Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ADT + RT 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. | 115 |
| TAK-700 + ADT + RT 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. | 116 |
| Total | 231 |
Baseline characteristics
| Characteristic | ADT + RT | Total | TAK-700 + ADT + RT |
|---|---|---|---|
| ADT Started Prior to Registration No | 31 Participants | 56 Participants | 25 Participants |
| ADT Started Prior to Registration Yes | 11 Participants | 31 Participants | 20 Participants |
| Age, Customized ≤ 49 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Customized 50 - 59 years | 16 Participants | 38 Participants | 22 Participants |
| Age, Customized 60 - 69 years | 44 Participants | 85 Participants | 41 Participants |
| Age, Customized ≥ 70 years | 53 Participants | 105 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 220 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Gleason Score 7 | 16 Participants | 34 Participants | 18 Participants |
| Gleason Score 8 | 37 Participants | 67 Participants | 30 Participants |
| Gleason Score ≥9 | 62 Participants | 130 Participants | 68 Participants |
| M-Stage M0 | 115 Participants | 231 Participants | 116 Participants |
| N-Stage N0 | 115 Participants | 231 Participants | 116 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 24 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) White | 93 Participants | 194 Participants | 101 Participants |
| Risk Factors Gleason 7, PSA ≥20-150, any T-stage | 14 Participants | 32 Participants | 18 Participants |
| Risk Factors Gleason 8, PSA ≥20-150, any T-stage | 13 Participants | 23 Participants | 10 Participants |
| Risk Factors Gleason 8, PSA <20, and ≥T2 | 23 Participants | 44 Participants | 21 Participants |
| Risk Factors Gleason ≥ 9, PSA ≤150, any T-stage | 65 Participants | 132 Participants | 67 Participants |
| RT Boost Modality High dose rate (HDR) implant | 0 Participants | 1 Participants | 1 Participants |
| RT Boost Modality Intensity-modulated radiation therapy (IMRT) | 103 Participants | 208 Participants | 105 Participants |
| RT Boost Modality Low dose rate (LDR) permanent prostate implant (PPI) | 12 Participants | 22 Participants | 10 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 115 Participants | 231 Participants | 116 Participants |
| Study Entry PSA 20.0-150.0 ng/ml | 40 Participants | 81 Participants | 41 Participants |
| Study Entry PSA < 20.0 ng/ml | 75 Participants | 150 Participants | 75 Participants |
| T-Stage T1a-T1c | 22 Participants | 45 Participants | 23 Participants |
| T-Stage T2-T2c | 66 Participants | 124 Participants | 58 Participants |
| T-Stage T3-T3b | 24 Participants | 57 Participants | 33 Participants |
| T-Stage T4 | 3 Participants | 5 Participants | 2 Participants |
| Zubrod Performance Status 0 | 99 Participants | 203 Participants | 104 Participants |
| Zubrod Performance Status 1 | 16 Participants | 28 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 115 | 19 / 116 |
| other Total, other adverse events | 108 / 112 | 112 / 115 |
| serious Total, serious adverse events | 19 / 112 | 38 / 115 |
Outcome results
Primary
Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)
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.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol) | 17.3 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol) | 12.8 percentage of participants |
Comparison: Revised protocol due to early accrual closure (September 2014) computes that seventy events with five years of additional follow-up after early accrual closure provides 70% power (at one-sided alpha = 0.05) to detect a 40% reduction in the assumed rate control arm rate of is 0.08/year.p-value: 0.5595% CI: [0.47, 1.48]Log Rank
Secondary
Change From Baseline in Body Mass Index (BMI)
Body Mass Index (BMI) is a person's weight in kilograms (or pounds) divided by the square of height in meters (or feet). Change from baseline = time point value - baseline value.
Time frame: Baseline and yearly to five years.
Population: Eligible participants data at baseline and data at any of the post-baseline timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Change From Baseline in Body Mass Index (BMI) | 2 years | 0.67 kg/m^2 | Standard Deviation 3.76 |
| ADT + RT | Change From Baseline in Body Mass Index (BMI) | 4 years | -0.02 kg/m^2 | Standard Deviation 6.95 |
| ADT + RT | Change From Baseline in Body Mass Index (BMI) | 3 years | 0.75 kg/m^2 | Standard Deviation 3.9 |
| ADT + RT | Change From Baseline in Body Mass Index (BMI) | 5 years | -0.52 kg/m^2 | Standard Deviation 3.01 |
| ADT + RT | Change From Baseline in Body Mass Index (BMI) | 1 year | 0.64 kg/m^2 | Standard Deviation 2.19 |
| TAK-700 + ADT + RT | Change From Baseline in Body Mass Index (BMI) | 5 years | 0.15 kg/m^2 | Standard Deviation 2.71 |
| TAK-700 + ADT + RT | Change From Baseline in Body Mass Index (BMI) | 1 year | -0.84 kg/m^2 | Standard Deviation 4.28 |
| TAK-700 + ADT + RT | Change From Baseline in Body Mass Index (BMI) | 2 years | -0.34 kg/m^2 | Standard Deviation 2.55 |
| TAK-700 + ADT + RT | Change From Baseline in Body Mass Index (BMI) | 3 years | 0.25 kg/m^2 | Standard Deviation 2.32 |
| TAK-700 + ADT + RT | Change From Baseline in Body Mass Index (BMI) | 4 years | 0.46 kg/m^2 | Standard Deviation 2.7 |
Secondary
Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year
The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year.
Time frame: Baseline, one year
Population: Eligible participants who consented to quality of life component and had baseline and one-year data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADT + RT | Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year | 2.78 T-score | Standard Deviation 7.21 |
| TAK-700 + ADT + RT | Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year | 3.16 T-score | Standard Deviation 8.24 |
Comparison: One hundred thirty evaluable participants (arms combined), provides 81% power to detect a moderate effect size of 0.5 using a two-sample test of the difference in means with a two-sided type I error of 0.05.p-value: 0.76t-test, 2 sided
Secondary
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year
The EPIC-Short Form is a 26-item, validated self-administered tool to assess disease-specific aspects of prostate cancer and its therapies consisting of five summary domains (bowel, urinary incontinence, urinary irritation/obstruction, sexual, and hormonal function). Responses for each item form a Likert scale which are transformed to a 0-100 scale. A domain score is the average of the transformed domain item scores, ranging from 0-100 with higher scores representing better health-related quality of life (HRQOL). Change at one year is defined as one-year value - baseline value. Positive change at one year indicates improved quality of life.
Time frame: Baseline, one year
Population: Eligible participants with data for any of the four domains.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Bowel domain | -5.45 score on a scale | Standard Deviation 9.1 |
| ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Sexual domain | -24.18 score on a scale | Standard Deviation 27.64 |
| ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Hormonal domain | -17.31 score on a scale | Standard Deviation 15.36 |
| ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Urinary domain | -1.67 score on a scale | Standard Deviation 13.9 |
| TAK-700 + ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Hormonal domain | -17.45 score on a scale | Standard Deviation 16.59 |
| TAK-700 + ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Bowel domain | -7.04 score on a scale | Standard Deviation 15.5 |
| TAK-700 + ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Urinary domain | -5.31 score on a scale | Standard Deviation 15.46 |
| TAK-700 + ADT + RT | Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year | Sexual domain | -27.26 score on a scale | Standard Deviation 25.98 |
Comparison: \[Bowel domain\] One hundred thirty evaluable participants (arms combined), provides 81% power to detect a moderate effect size of 0.5 using a two-sample test of the difference in means with a two-sided type I error of 0.05.p-value: 0.44t-test, 2 sided
Comparison: \[Urinary domain\] One hundred thirty evaluable participants (arms combined), provides 81% power to detect a moderate effect size of 0.5 using a two-sample test of the difference in means with a two-sided type I error of 0.05.p-value: 0.13t-test, 2 sided
Comparison: \[Sexual domain\] One hundred thirty evaluable participants (arms combined), provides 81% power to detect a moderate effect size of 0.5 using a two-sample test of the difference in means with a two-sided type I error of 0.05.p-value: 0.5t-test, 2 sided
Comparison: \[Hormonal domain\] One hundred thirty evaluable participants (arms combined), provides 81% power to detect a moderate effect size of 0.5 using a two-sample test of the difference in means with a two-sided type I error of 0.05.p-value: 0.96t-test, 2 sided
Secondary
Fasting Plasma Glucose
Time frame: Baseline, 12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Fasting Plasma Glucose | 12 months | 102.27 mg/dL | Standard Deviation 53.06 |
| ADT + RT | Fasting Plasma Glucose | 24 months | 104.24 mg/dL | Standard Deviation 67.43 |
| ADT + RT | Fasting Plasma Glucose | Baseline | 98.99 mg/dL | Standard Deviation 51.87 |
| TAK-700 + ADT + RT | Fasting Plasma Glucose | 24 months | 105.51 mg/dL | Standard Deviation 40.53 |
| TAK-700 + ADT + RT | Fasting Plasma Glucose | Baseline | 100.52 mg/dL | Standard Deviation 45.54 |
| TAK-700 + ADT + RT | Fasting Plasma Glucose | 12 months | 117.39 mg/dL | Standard Deviation 118.4 |
Secondary
Fasting Plasma Insulin
Time frame: Baseline, 12 months, 24 months
Population: This data was not collected.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Fasting Plasma Insulin | Baseline | — |
| Unknown | Fasting Plasma Insulin | 12 months | — |
| Unknown | Fasting Plasma Insulin | 24 months | — |
Secondary
Fasting Total Cholesterol
Time frame: Baseline, 12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Fasting Total Cholesterol | Baseline | 149.71 mg/dL | Standard Deviation 68.2 |
| ADT + RT | Fasting Total Cholesterol | 12 months | 160.27 mg/dL | Standard Deviation 73.22 |
| ADT + RT | Fasting Total Cholesterol | 24 months | 163.20 mg/dL | Standard Deviation 168.63 |
| TAK-700 + ADT + RT | Fasting Total Cholesterol | Baseline | 154.20 mg/dL | Standard Deviation 71.05 |
| TAK-700 + ADT + RT | Fasting Total Cholesterol | 12 months | 154.74 mg/dL | Standard Deviation 70.85 |
| TAK-700 + ADT + RT | Fasting Total Cholesterol | 24 months | 160.61 mg/dL | Standard Deviation 77.55 |
Secondary
Hemoglobin A1c
Time frame: Baseline, 12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Hemoglobin A1c | Baseline | 6.12 g/dL | Standard Deviation 1.05 |
| ADT + RT | Hemoglobin A1c | 12 months | 6.33 g/dL | Standard Deviation 1.18 |
| ADT + RT | Hemoglobin A1c | 24 months | 6.30 g/dL | Standard Deviation 1.59 |
| TAK-700 + ADT + RT | Hemoglobin A1c | Baseline | 6.01 g/dL | Standard Deviation 1.05 |
| TAK-700 + ADT + RT | Hemoglobin A1c | 12 months | 5.95 g/dL | Standard Deviation 0.73 |
| TAK-700 + ADT + RT | Hemoglobin A1c | 24 months | 6.04 g/dL | Standard Deviation 0.76 |
Secondary
Median Testosterone Recovery Time
Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Testosterone recovery rates are estimated using the Kaplan-Meier method, censoring for biochemical, local, or distant failure, salvage therapy, death, and otherwise alive without event. Testosterone recovery time is defined as time from randomization to testosterone recovery or censoring.
Time frame: 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.
Population: Eligible participants with testosterone data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADT + RT | Median Testosterone Recovery Time | NA years |
| TAK-700 + ADT + RT | Median Testosterone Recovery Time | NA years |
p-value: 0.010495% CI: [0.29, 0.89]Log Rank
Secondary
Number of Participants by Highest Grade Adverse Event
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data
Time frame: 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.
Population: Eligible participants who started protocol treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 2 | 54 Participants |
| ADT + RT | Number of Participants by Highest Grade Adverse Event | Garde 4 | 4 Participants |
| ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 1 | 17 Participants |
| ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 5 | 3 Participants |
| ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 3 | 31 Participants |
| TAK-700 + ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 5 | 1 Participants |
| TAK-700 + ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 1 | 2 Participants |
| TAK-700 + ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 2 | 45 Participants |
| TAK-700 + ADT + RT | Number of Participants by Highest Grade Adverse Event | Grade 3 | 55 Participants |
| TAK-700 + ADT + RT | Number of Participants by Highest Grade Adverse Event | Garde 4 | 9 Participants |
Secondary
Number of Patients With Clinical Survivorship Events
Clinical survivorship events are defined as the following newly diagnosed non-fatal cardiovascular events or other clinical endpoints relevant to prostate cancer survivorship: type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and osteoporotic fracture.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADT + RT | Number of Patients With Clinical Survivorship Events | Myocardial infarction | 6 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Pulmonary embolism | 10 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Coronary artery disease | 16 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Deep vein thrombosis | 8 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Stroke | 5 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Osteoporotic fracture | 6 Participants |
| ADT + RT | Number of Patients With Clinical Survivorship Events | Type 2 diabetes | 30 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Osteoporotic fracture | 1 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Type 2 diabetes | 18 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Coronary artery disease | 14 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Myocardial infarction | 8 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Stroke | 6 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Pulmonary embolism | 5 Participants |
| TAK-700 + ADT + RT | Number of Patients With Clinical Survivorship Events | Deep vein thrombosis | 7 Participants |
Secondary
Percentage of Participants With Death Due to Prostate Cancer
Time to prostate cancer death is defined as time from randomization to the date of death due to prostate cancer, last known follow-up (censored), or death due to other causes (competing risk). Failure rates were to be estimated using the cumulative incidence method. If too few events occur for meaningful estimates, then only counts of events will be reported.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With Death Due to Prostate Cancer | 7.7 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With Death Due to Prostate Cancer | 4.9 percentage of participants |
Secondary
Percentage of Participants With Distant Metastases
Distant metastases (failure) is defined as imaging or biopsy demonstrated evidence for systemic recurrence. Biopsy was not required, however it was encouraged in absence of a rising PSA. 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. Note, the protocol lists this endpoint as regional or distant metastasis, but regional progression data was not collected.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With Distant Metastases | 6.8 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With Distant Metastases | 2.9 percentage of participants |
Comparison: Revised protocol due to early accrual closure (September 2014) computes that 5-year survival of 78% and annual hazard rate of 0.02 for ADT + RT arm, with five years of additional follow-up after early accrual closure provides 32% power (at two-sided alpha = 0.05) to detect a 50% reduction in failure rate.p-value: 0.4895% CI: [0.29, 1.75]Log Rank
Secondary
Percentage of Participants With General Clinical Treatment Failure
General clinical treatment failure (GCTF) is defined as: PSA \> 25 ng/ml, documented local disease progression, regional or distant metastasis, or initiation of salvage androgen deprivation therapy. Failure time is defined as time from registration to the date of 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.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With General Clinical Treatment Failure | 12.5 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With General Clinical Treatment Failure | 6.8 percentage of participants |
p-value: 0.6595% CI: [0.45, 1.63]Log Rank
Secondary
Percentage of Participants With Grade 3 or Higher Adverse Events
Time to grade 3 or higher adverse event (event) is defined as time from randomization to the date of first event, last known follow-up (censored), or death without failure (competing risk). Event 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.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With Grade 3 or Higher Adverse Events | 34.9 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With Grade 3 or Higher Adverse Events | 58.9 percentage of participants |
p-value: <0.00195% CI: [1.54, 3.4]Log Rank
Secondary
Percentage of Participants With Local Progression
Local recurrence (failure) is defined as biopsy proven recurrence within the prostate gland. Time to failure is defined as time from randomization to the date of 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.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Participants With Local Progression | 2.9 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Participants With Local Progression | 0.0 percentage of participants |
p-value: 0.9995% CI: [0.33, 3.13]Log Rank
Secondary
Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol)
Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from primary (original protocol) to secondary. Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.
Time frame: 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.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADT + RT | Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol) | 89.4 percentage of participants |
| TAK-700 + ADT + RT | Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol) | 88.1 percentage of participants |
Comparison: Revised protocol due to early accrual closure (September 2014) computes that 5-year survival of 78% and annual hazard rate of 0.055 for ADT + RT arm, with five years of additional follow-up after early accrual closure provides 28% power (at two-sided alpha = 0.05) to detect a 33% reduction in failure rate.p-value: 0.2795% CI: [0.38, 1.31]Log Rank
Secondary
Serum High-density Lipoprotein (HDL)
Time frame: Baseline, 12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Serum High-density Lipoprotein (HDL) | Baseline | 40.91 mg/dL | Standard Deviation 20.96 |
| ADT + RT | Serum High-density Lipoprotein (HDL) | 12 months | 44.94 mg/dL | Standard Deviation 24.21 |
| ADT + RT | Serum High-density Lipoprotein (HDL) | 24 months | 42.16 mg/dL | Standard Deviation 23.77 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (HDL) | Baseline | 41.32 mg/dL | Standard Deviation 20.93 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (HDL) | 12 months | 44.50 mg/dL | Standard Deviation 24.21 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (HDL) | 24 months | 44.85 mg/dL | Standard Deviation 23.36 |
Secondary
Serum High-density Lipoprotein (LDL)
Time frame: Baseline, 12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Serum High-density Lipoprotein (LDL) | Baseline | 88.78 mg/dL | Standard Deviation 45.64 |
| ADT + RT | Serum High-density Lipoprotein (LDL) | 12 months | 86.18 mg/dL | Standard Deviation 47.11 |
| ADT + RT | Serum High-density Lipoprotein (LDL) | 24 months | 81.35 mg/dL | Standard Deviation 47.73 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (LDL) | Baseline | 87.85 mg/dL | Standard Deviation 47.33 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (LDL) | 12 months | 83.73 mg/dL | Standard Deviation 46.86 |
| TAK-700 + ADT + RT | Serum High-density Lipoprotein (LDL) | 24 months | 95.34 mg/dL | Standard Deviation 59.22 |
Secondary
Serum Testosterone
Time frame: Baseline,12 months, 24 months
Population: Eligible participants with data at any of the timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADT + RT | Serum Testosterone | Baseline | 355.75 ng/dL | Standard Deviation 225.65 |
| ADT + RT | Serum Testosterone | 12 months | 35.68 ng/dL | Standard Deviation 68.39 |
| ADT + RT | Serum Testosterone | 24 months | 86.47 ng/dL | Standard Deviation 182.4 |
| TAK-700 + ADT + RT | Serum Testosterone | Baseline | 357.73 ng/dL | Standard Deviation 217.26 |
| TAK-700 + ADT + RT | Serum Testosterone | 12 months | 25.22 ng/dL | Standard Deviation 67.49 |
| TAK-700 + ADT + RT | Serum Testosterone | 24 months | 17.36 ng/dL | Standard Deviation 32.71 |
Secondary
Testosterone Recovery at 12 and 24 Months
Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Time to testosterone recovery is defined as time from randomization to the date of testosterone recovery, biochemical, local, or distant failure (competing risk), salvage therapy (competing risk), death (competing risk), or last known follow-up (censored). Testosterone recovery rates are estimated using the cumulative incidence method.
Time frame: 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.
Population: Eligible participants with testosterone data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ADT + RT | Testosterone Recovery at 12 and 24 Months | 12 months | 19.4 percentage of participants |
| ADT + RT | Testosterone Recovery at 12 and 24 Months | 24 months | 32.9 percentage of participants |
| TAK-700 + ADT + RT | Testosterone Recovery at 12 and 24 Months | 12 months | 12.5 percentage of participants |
| TAK-700 + ADT + RT | Testosterone Recovery at 12 and 24 Months | 24 months | 17.4 percentage of participants |