Prostatic Neoplasms
Conditions
Brief summary
The purpose of this study is to compare the improvement in time to prostate specific antigen (PSA) progression (TTPP, as defined by Prostate Cancer Working Group 2 \[PCWG2\]) of apalutamide versus placebo in Chinese participants with high-risk non-metastatic castration resistant prostate cancer (NM-CRPC).
Interventions
DRUGApalutamide
Apalutamide 240 mg (4\*60 mg tablets) will be administrated orally once daily.
DRUGPlacebo
Matching placebo will be administered orally.
Participants will continue to receive ADT with gonadotrophin-releasing hormone agonists (GnRHa) who have not been surgically castrated.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equals to (\<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous androgen deprivation therapy (ADT) * Castration-resistant prostate cancer (PC) demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA greater than (\>) 2 nanogram per milliliter (ng/mL) * Surgically or medically castrated, with testosterone levels of less than (\<) 50 nanogram per deciliter (ng/dL). If the participant is medically castrated, continuous dosing with gonadotropin releasing hormone analog (GnRHa) must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone * Participants who received a first-generation anti-androgen (example: bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization and must show continuing disease progression (an increase in PSA) after washout * At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
Exclusion criteria
* Presence of distant metastases, including central nervous system (CNS) and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes \<2 centimeter in short axis (N1) located below the iliac bifurcation are allowed * Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis, due to primary tumor (example, tumor obstruction of bladder trigone) * Prior treatment with cytochrome P450 17 alpha-hydroxylase/17,20-lyase (CYP17) inhibitors (example: abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide) for PC * Prior chemotherapy for PC, except if administered in the adjuvant/neoadjuvant setting * Prior treatment with second generation anti-androgens (example, enzalutamide) * History of seizure or condition that may pre-dispose to seizure (example: prior stroke within 1 year prior to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria | From randomization until first documented PSA progression (up to 3 years 3 months) | Time to prostate specific antigen progression (TTPP) was defined as the time from randomization to the first date of documented PSA progression based on PCWG2 criteria. PCWG2 was defined as the PSA progression as 1) the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) or more from the Nadir was documented, which was confirmed by a second value obtained 3 or more weeks later. 2) Where no decline from baseline was documented as a 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 week of treatment. Kaplan-Meier method was used for the analysis. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Up to 6 years 4 months |
| Number of Participants With Grade 3 or Higher Abnormalities in Laboratory Values | Up to 6 years 4 months |
| Percentage of Participants Who Achieved Prostate Specific Antigen (PSA) Response (>=50% PSA Reduction) | Up to 6 years 4 months |
| Plasma Concentration of Apalutamide and Its Metabolite (N-desmethyl Apalutamide) | Presdose: Day 1 of Cycles 1, 2, 3, and 6; 2 hours postdose: Day 1 of Cycles 1 and 3 |
Countries
China
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Results are currently reported till primary completion date (01 Jun 2023). Post completing end of treatment (EoT, 30 days after last dose of study treatment) visit, participants entered post-treatment followup phase and remained in study until death, recording of development of symptomatic progression, initiation of any new systemic anticancer therapies, withdrawal of consent or study termination. Follow-up phase is still ongoing and thus remaining results will be posted upon study completion.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Plus Androgen-deprivation Therapy (ADT) Participants received placebo matching to apalutamide tablets orally once daily along with ADT of Cycle 1 Day 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study. Each treatment cycle was of 28 days. Participants who did not have distant metastasis were switched to receive apalutamide + ADT from Cycle 6 Day 1 and those who had prostate-specific antigen (PSA) prior to completion of first 5 cycles crossed over to receive apalutamide + ADT at the time of PSA progression. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study by the sponsor. | 25 |
| Apalutamide 240 mg Plus ADT Participants received apalutamide 240 milligrams (mg) tablets (4 tablets of 60 mg) orally once daily along with ADT from Cycle 1 Day 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study. Each treatment cycle was of 28 days. | 50 |
| Total | 75 |
Baseline characteristics
| Characteristic | Placebo Plus Androgen-deprivation Therapy (ADT) | Total | Apalutamide 240 mg Plus ADT |
|---|---|---|---|
| Age, Continuous | 74.5 Years STANDARD_DEVIATION 7.82 | 74.9 Years STANDARD_DEVIATION 7.83 | 75.1 Years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 75 Participants | 50 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 25 Participants | 75 Participants | 50 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 25 Participants | 75 Participants | 50 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 | 1 / 25 | 4 / 50 | 0 / 22 | 4 / 72 |
| other Total, other adverse events | 11 / 25 | 47 / 50 | 21 / 22 | 68 / 72 |
| serious Total, serious adverse events | 4 / 25 | 20 / 50 | 5 / 22 | 25 / 72 |
Outcome results
Primary
Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria
Time to prostate specific antigen progression (TTPP) was defined as the time from randomization to the first date of documented PSA progression based on PCWG2 criteria. PCWG2 was defined as the PSA progression as 1) the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) or more from the Nadir was documented, which was confirmed by a second value obtained 3 or more weeks later. 2) Where no decline from baseline was documented as a 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 week of treatment. Kaplan-Meier method was used for the analysis.
Time frame: From randomization until first documented PSA progression (up to 3 years 3 months)
Population: The Intent-to-Treat (ITT) analysis set included all randomized participants and were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus Androgen-deprivation Therapy (ADT) | Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria | NA Months |
| Apalutamide 240 mg Plus ADT | Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria | NA Months |
p-value: =0.005295% CI: [0.077, 0.705]Log Rank
Secondary
Number of Participants With Grade 3 or Higher Abnormalities in Laboratory Values
Time frame: Up to 6 years 4 months
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: Up to 6 years 4 months
Secondary
Percentage of Participants Who Achieved Prostate Specific Antigen (PSA) Response (>=50% PSA Reduction)
Time frame: Up to 6 years 4 months
Secondary
Plasma Concentration of Apalutamide and Its Metabolite (N-desmethyl Apalutamide)
Time frame: Presdose: Day 1 of Cycles 1, 2, 3, and 6; 2 hours postdose: Day 1 of Cycles 1 and 3