Prostate Cancer
Conditions
Keywords
abiraterone acetate, apalutamide, leuprolide, prednisone, neoadjuvant therapy
Brief summary
This multicenter randomized phase II trial investigates the impact of intense androgen deprivation on radical prostatectomy (RP) pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).
Detailed description
This is a multicenter, phase II, prospective, randomized trial designed to investigate the efficacy of neoadjuvant and adjuvant abiraterone acetate + apalutamide for men with intermediate-high risk prostate cancer who are candidates for RP. The study includes two parts. In part 1, patients will be randomized in 1:1 ratio to receive 6 months of abiraterone acetate, apalutamide, leuprolide and prednisone (Arm 1A) versus 6 months of abiraterone acetate, leuprolide and prednisone (Arm 1B) followed by RP, stratified by risk factor (intermediate versus high-risk). High-risk factors will be defined as a Gleason score ≥ 8, PSA \> 20 ng/dL, or T3 disease on MRI. In part 2 (post-RP), patients will be randomized in 1:1 ratio to receive an additional 12 months of abiraterone acetate, apalutamide, leuprolide and prednisone (Arm 2A) or observation (Arm 2B) stratified by type of neoadjuvant therapy and pathological T-stage (\< pT3 versus ≥ pT3) after RP but before cycle 7 day 1 following neoadjuvant therapy. There will be an early stopping rule for Part 2 should a high rate of patients refuse to participate or drop out early while receiving adjuvant therapy (\<6 months).
Interventions
DRUGApalutamide
DRUGLeuprolide
DRUGPrednisone
DRUGAbiraterone Acetate
Sponsors
Janssen Scientific Affairs, LLC
Dana-Farber Cancer Institute
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. Male ≥ 18 years of age. 2. Histologically confirmed adenocarcinoma of the prostate without histological variants comprising \>50% of the sample as determined by academic center central review (including neuroendocrine differentiation, small cell, sarcomatoid, ductal adenocarcinoma, squamous or transitional cell carcinoma). 3. Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within seven months from screening. Less than 3 core biopsies are allowed if the patient has \>1 cm or T3 disease on MRI. 4. Patients must have the following features: * Gleason ≥ 4+3=7 OR * Gleason 3+4=7 AND at least one of the following: PSA \>20 ng/dL or T3 disease (as determined by MRI). 5. No evidence of metastatic disease as determined by radionuclide bone scans and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis. 6. Participants must be candidates for RP and considered surgically resectable by urologic evaluation. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 8. Participants must have normal organ and marrow function as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,500/mcL * Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start * Serum potassium ≥ 3.5 mmol/L * Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible) * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN * Serum albumin ≥ 3.0 g/dL * Serum creatinine \< 2.0 x ULN * PTT≤60 9. Participant must agree to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or must agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Participant must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. 10. Medications known to lower the seizure threshold (see list under APPENDIX D: Representative Medications that May Predispose to Seizure) must be discontinued or substituted at least 1 week prior to study treatment.
Exclusion criteria
1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, Apalutamide and others), CYP17 inhibitors (including abiraterone acetate, TAK-700, galeterone, ketoconazole, and others), estrogens, Luteinizing Hormone Releasing Hormone (LHRH) agonist/antagonists. Prior therapy with 5α-reductase inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1. 2. Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer. 3. Prior systemic treatment with an azole drug within two weeks of start of treatment. 4. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone \< 200 ng/dL. 5. Clinically significant cardiovascular disease within 6 months of study treatment including: * Severe or unstable angina; * Myocardial infarction; * Symptomatic congestive heart failure; * New York Heart Association (NYHA) class II-IV heart disease; * Arterial or venous thromboembolic events (such as pulmonary embolism cerebrovascular accident including transient ischemic attacks); * History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes); * Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG \> 470 msec; * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; * Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy. 6. History of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs. 8. Severe hepatic impairment (Child-Pugh Class C). 9. Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated. 10. History of pituitary or adrenal dysfunction. 11. Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug. 12. Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular, or inhaled corticosteroids are permitted. 13. Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide. 14. Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin. 15. Major surgery or radiation therapy within 30 days of screening visit. Participants who have had a major surgery within 30 days of screening visit may be eligible provided the treating investigator deems that the participant is at low risk for complications. 16. Any condition that in the opinion of the investigator would preclude participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined pCR or MRD Rate [Part 1] | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | Pathological response, defined as achieving either pCR or MRD at radical prostatectomy (RP). Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen. MRD will be defined as residual tumor in the RP specimen measuring ≤ 5 mm. |
| Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2] | At 3 years post RP | 3-year bPFS rate is defined as the probability of biochemical progression free and survival at 3 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 3-year mark are censored at date last disease evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Presenting Cribriform at RP (Part 1) | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | Presence or cribriform was evaluated by central pathology review of specimens at radical prostatectomy (RP). |
| Frequency of Presenting Intraductal Carcinoma at RP (Part 1) | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | Intraductal carcinoma was evaluated by central pathology review of specimens at Radical Prostatectomy (RP). |
| Frequency of Positive Surgical Margins at RP (Part 1) | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | Pathologic specimens were centrally reviewed and counted for positive surgical margins at the time of Radical Prostatectomy (RP). |
| Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1) | Assessed on day 1 of each cycle (1 cycle=28 +/- 2 days), up to 6 months from the initiation of neoadjuvant therapy. | Prostate specific antigen (PSA) was measured on day 1 of each cycle during the neoadjuvant therapy. PSA nadir was defined as the lowest PSA value prior to Radical Prostatectomy (RP). Number and percent of participants with nadir PSA \< 0.2 ng/mL were reported. |
| Frequency of Presenting Intra-operative Complications Following RP (Part 1) | Assessed post-RP, at 6 months from the initiation of neoadjuvant therapy. | Intra-operative complications were collected via questionnaire following Radical Prostatectomy. |
| Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2] | At 2 years post RP | 2-year bPFS rate is defined as the probability of biochemical progression free and survival at 2 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 2-year mark are censored at date of last disease evaluation. |
| Rate of pCR at RP (Part 1) | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen at radical prostatectomy (RP). |
| Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2) | At 2-years post RP | Defined as the probability of freedom from further anti-cancer therapy at 2-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 2-year mark are censored at date of last follow-up. |
| Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2) | At 3 years post RP | Defined as the probability of freedom from further anti-cancer therapy at 3-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 3-year mark are censored at date of last follow-up. |
| Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2) | At 4-years post RP | Defined as the probability of freedom from further anti-cancer therapy at 4-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 4-year mark are censored at date of last follow-up. |
| Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | At 6-months post-RP | The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL. |
| Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | At 12-months post-RP | The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL. |
| Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | At 24-months post-RP | The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL. |
| Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2] | At 4 years post RP | 4-year bPFS rate is defined as the probability of biochemical progression free and survival at 4 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 4-year mark are censored at date of last disease evaluation. |
| Median of Residual Cancer Burden (RCB) at RP (Part 1) | Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy. | RCB was calculated as tumor volume (cm\^3) X % cellularity. RCB was analyzed as a continuous score (with median and range) instead of a categorical variable based on the percentile cutoff point, at the time of radical prostatectomy (RP). |
Countries
United States
Participant flow
Recruitment details
This is a 2-part study: In part 1, patients will be randomized in 1:1 ratio to receive 6 months of AAPL (Arm 1A) versus 6 months of APL (Arm 1B) followed by RP, stratified by risk factor. In part 2 (post-RP), patients will be randomized in 1:1 ratio to receive an additional 12 months of AAPL (Arm 2A) or observation (Arm 2B) stratified by type of neoadjuvant therapy and pathological T-stage after RP but before cycle 7 day 1 following neoadjuvant therapy.
Pre-assignment details
The part 2 of the study is still in progression and the final data has not been collected
Participants by arm
| Arm | Count |
|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) Eligible Participants will be randomized to receive:
AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 months | 59 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) Eligible Participants will be randomized to receive:
APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months | 59 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 | Adverse Event | 3 | 0 | 0 | 0 |
| Part 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Part 2 | Adverse Event | 0 | 0 | 5 | 0 |
| Part 2 | Subject withdrew after 6 cycles of protocol therapy. | 0 | 0 | 1 | 0 |
| Part 2 | Subject withdrew after part-2 randomization and received non-protocol therapy. | 0 | 0 | 1 | 2 |
| Part 2 | Subject withdrew after part-2 randomization and remained on observation. | 0 | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Arm 1B: APL Neoadjuvant Therapy (Part 1) | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 58 years | 61 years |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 6 participants | 9 participants |
| Race/Ethnicity, Customized Other | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized White | 55 participants | 48 participants | 103 participants |
| Region of Enrollment United States | 59 participants | 59 participants | 118 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 59 Participants | 59 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 59 | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 59 / 59 | 59 / 59 | 30 / 37 | 28 / 38 |
| serious Total, serious adverse events | 8 / 59 | 5 / 59 | 4 / 37 | 0 / 38 |
Outcome results
Primary
Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2]
3-year bPFS rate is defined as the probability of biochemical progression free and survival at 3 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 3-year mark are censored at date last disease evaluation.
Time frame: At 3 years post RP
Population: The primary efficacy analysis was the intent-to-treat approach, including all patients who have been randomized into Part 2 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2] | 81 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2] | 72 percentage of subjects |
Primary
Combined pCR or MRD Rate [Part 1]
Pathological response, defined as achieving either pCR or MRD at radical prostatectomy (RP). Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen. MRD will be defined as residual tumor in the RP specimen measuring ≤ 5 mm.
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Combined pCR or MRD Rate [Part 1] | 12 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Combined pCR or MRD Rate [Part 1] | 12 Participants |
Secondary
Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2]
2-year bPFS rate is defined as the probability of biochemical progression free and survival at 2 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 2-year mark are censored at date of last disease evaluation.
Time frame: At 2 years post RP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2] | 90 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2] | 80 percentage of subjects |
Secondary
Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2]
4-year bPFS rate is defined as the probability of biochemical progression free and survival at 4 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 4-year mark are censored at date of last disease evaluation.
Time frame: At 4 years post RP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2] | 67 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2] | 61 percentage of subjects |
Secondary
Frequency of Positive Surgical Margins at RP (Part 1)
Pathologic specimens were centrally reviewed and counted for positive surgical margins at the time of Radical Prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Frequency of Positive Surgical Margins at RP (Part 1) | 4 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Frequency of Positive Surgical Margins at RP (Part 1) | 7 Participants |
Secondary
Frequency of Presenting Cribriform at RP (Part 1)
Presence or cribriform was evaluated by central pathology review of specimens at radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Cribriform at RP (Part 1) | 1 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Cribriform at RP (Part 1) | 0 Participants |
Secondary
Frequency of Presenting Intraductal Carcinoma at RP (Part 1)
Intraductal carcinoma was evaluated by central pathology review of specimens at Radical Prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Intraductal Carcinoma at RP (Part 1) | 15 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Intraductal Carcinoma at RP (Part 1) | 19 Participants |
Secondary
Frequency of Presenting Intra-operative Complications Following RP (Part 1)
Intra-operative complications were collected via questionnaire following Radical Prostatectomy.
Time frame: Assessed post-RP, at 6 months from the initiation of neoadjuvant therapy.
Population: Assessed in 114 patients (55 in AAPL Arm and 59 in APL Arm) who received RP, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Intra-operative Complications Following RP (Part 1) | 1 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Frequency of Presenting Intra-operative Complications Following RP (Part 1) | 1 Participants |
Secondary
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 12-months post-RP
Population: 32 subjects receiving Arm 2A and 39 receiving Arm 2B completed EPIC-26 QOL questionnaires at 12 months post RP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Urinary Incontinence | 75 score on 0-100 scale | Standard Deviation 24 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Sexual | 16 score on 0-100 scale | Standard Deviation 18 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Bowel | 95 score on 0-100 scale | Standard Deviation 12 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Hormonal | 68 score on 0-100 scale | Standard Deviation 22 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Urinary Irritative | 91 score on 0-100 scale | Standard Deviation 11 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Hormonal | 86 score on 0-100 scale | Standard Deviation 15 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Urinary Irritative | 91 score on 0-100 scale | Standard Deviation 10 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Urinary Incontinence | 74 score on 0-100 scale | Standard Deviation 25 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Bowel | 94 score on 0-100 scale | Standard Deviation 12 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2) | Sexual | 26 score on 0-100 scale | Standard Deviation 26 |
Secondary
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 24-months post-RP
Population: 14 subjects receiving Arm 2A and 12 receiving Arm 2B completed EPIC-26 QOL questionnaires at 24 months post RP. The QOL questionnaire completion rate was low at the 24-month visit. Due to the Covid19 pandemic, many follow-up visits were conducted virtually. These questionnaires were done when possible and the patients were back in the clinic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Hormonal | 88 score on 0-100 scale | Standard Deviation 20 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Urinary Irritative | 92 score on 0-100 scale | Standard Deviation 12 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Urinary Incontinence | 75 score on 0-100 scale | Standard Deviation 22 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Bowel | 95 score on 0-100 scale | Standard Deviation 12 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Sexual | 31 score on 0-100 scale | Standard Deviation 31 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Sexual | 26 score on 0-100 scale | Standard Deviation 30 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Bowel | 97 score on 0-100 scale | Standard Deviation 4 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Urinary Irritative | 93 score on 0-100 scale | Standard Deviation 9 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Hormonal | 90 score on 0-100 scale | Standard Deviation 8 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2) | Urinary Incontinence | 76 score on 0-100 scale | Standard Deviation 30 |
Secondary
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 6-months post-RP
Population: 32 subjects receiving Arm 2A and 34 receiving Arm 2B completed EPIC-26 QOL questionnaires at 6 months post RP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Urinary Incontinence | 63 Score on 0-100 | Standard Deviation 24 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Sexual | 17 Score on 0-100 | Standard Deviation 19 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Bowel | 95 Score on 0-100 | Standard Deviation 11 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Hormonal | 68 Score on 0-100 | Standard Deviation 20 |
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Urinary Irritative | 90 Score on 0-100 | Standard Deviation 11 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Hormonal | 83 Score on 0-100 | Standard Deviation 16 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Urinary Irritative | 92 Score on 0-100 | Standard Deviation 8 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Urinary Incontinence | 72 Score on 0-100 | Standard Deviation 23 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Bowel | 96 Score on 0-100 | Standard Deviation 7 |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2) | Sexual | 14 Score on 0-100 | Standard Deviation 14 |
Secondary
Median of Residual Cancer Burden (RCB) at RP (Part 1)
RCB was calculated as tumor volume (cm\^3) X % cellularity. RCB was analyzed as a continuous score (with median and range) instead of a categorical variable based on the percentile cutoff point, at the time of radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Median of Residual Cancer Burden (RCB) at RP (Part 1) | 0.023 (cm^3) * % |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Median of Residual Cancer Burden (RCB) at RP (Part 1) | 0.075 (cm^3) * % |
Secondary
Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1)
Prostate specific antigen (PSA) was measured on day 1 of each cycle during the neoadjuvant therapy. PSA nadir was defined as the lowest PSA value prior to Radical Prostatectomy (RP). Number and percent of participants with nadir PSA \< 0.2 ng/mL were reported.
Time frame: Assessed on day 1 of each cycle (1 cycle=28 +/- 2 days), up to 6 months from the initiation of neoadjuvant therapy.
Population: PSA nadir was collected in 115 patients (56 in AAPL Arm and 59 in APL Arm).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1) | 55 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1) | 58 Participants |
Secondary
Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 2-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 2-year mark are censored at date of last follow-up.
Time frame: At 2-years post RP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2) | 90 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2) | 80 percentage of subjects |
Secondary
Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 3-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 3-year mark are censored at date of last follow-up.
Time frame: At 3 years post RP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2) | 83 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2) | 72 percentage of subjects |
Secondary
Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 4-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 4-year mark are censored at date of last follow-up.
Time frame: At 4-years post RP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2) | 78 percentage of subjects |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2) | 67 percentage of subjects |
Secondary
Rate of pCR at RP (Part 1)
Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen at radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Population: 114 patients (55 in AAPL Arm and 59 in APL Arm) had RP pathologic assessment, excluding the four who withdrew prior to RP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy (Part 1) | Rate of pCR at RP (Part 1) | 7 Participants |
| Arm 1B: APL Neoadjuvant Therapy (Part 1) | Rate of pCR at RP (Part 1) | 6 Participants |