Prostatic Neoplasms
Conditions
Brief summary
Main Study: The purpose of main study is to assess if the combination of apalutamide and androgen deprivation therapy (ADT) in participants with high-risk localized prostate cancer improves the biochemical recurrence (BCR) free rate. Sub-study: The purpose of the sub-study is to assess if the co administration of apalutamide and relugolix is able to maintain castrate levels of testosterone.
Interventions
DRUGApalutamide
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) oral tablets during the main study and sub-study.
DRUGADT
Participants will receive ADT intramuscular or subcutaneously during the main study.
DRUGRelugolix
Participants will receive 120 mg of relugolix following a loading dose of 360 mg of (3 tablets of 120 mg each) relugolix during the sub-study.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A candidate for radical prostatectomy (RP) or status post RP. Eligible to receive study intervention between Day 29 and Day 90 post-RP. Post RP prostate-specific antigen (PSA) of \<= 0.2 nanograms per milliliter (ng/mL). Has not received other treatment for prostate cancer * Have recovered from RP procedure and have had no worsening in cardiac risk in the peri-operative period per the clinical judgement of the investigator * Adequate organ function (hepatic, renal, hematologic and cerebral) determined at the discretion of the treating physician * Eastern Cooperative oncology Group (ECOG) Performance Status Score of 0 or 1 * Histologically confirmed adenocarcinoma of the prostate and categorized as high risk for recurrent prostate cancer. High risk can be defined based on PSA alone or biopsy or RP specimen as follows: PSA greater than or equal to (\>=) 20 ng/ml or; Gleason Score \>= 9 in any core on biopsy or; Gleason Score \>= 8 (4+4 or 5+3) in greater than (\>) 80 percentage (%) of 2 cores on biopsy or; Gleason Score = 8 (4+4 or 5+3) in 1 core as long 5 or more other cores with minimum Gleason Score of 4+3 on biopsy. The determination of high risk may be based on pathology report of biopsy or equivalent criteria from radical prostatectomy
Exclusion criteria
* History or presence of soft tissue/bone metastasis or metastasis in distant lymph nodes (pelvic lymph nodes below the iliac bifurcation that are less than (\<) 2 centimeter (cm) in diameter \[short axis\] either radiographically or pathologically are allowed.) * History of bilateral orchiectomy * Received an investigational intervention \<= 4 weeks before the planned first dose of study intervention * History of seizure or any condition that in the opinion of the investigator may predispose to seizure or treatment with drugs known to lower the seizure threshold within 4 weeks prior to starting treatment with apalutamide * Allergy or hypersensitivity to apalutamide, or excipients, unable or unwilling to take androgen deprivation therapy (ADT)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 24 | At Month 24 | Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed prostate specific antigen (PSA) greater than (\>) 0.2 nanogram per milliliter (ng/mL). Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study. |
| Sub-study: Percentage of Participants Who Maintained Testosterone Level Less Than (<) 50 Nanograms Per Deciliter (ng/dL) Through Day 28 | From Day -14 through Day 28 | Percentage of participants maintaining testosterone level \<50 ng/dL through Day 28 were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 12 | At Month 12 | Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed PSA \>0.2 ng/mL. Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study. |
| Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24 | At Months 18 and 24 | Percentage of participants with serum testosterone recovery (\>=150 ng/dL) at Months 18 and 24 were reported. Testosterone recovery was defined as a serum testosterone level greater than or equal to (\>=)150 nanograms per deciliter (ng/dL). |
| Sub-study: Number of Participants With Treatment-emergent Adverse Events | From 1st dose of study intervention (relugolix on Day -14) up to end of sub-study (Day 28) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and it does not necessarily have a causal relationship with the intervention. TEAEs were defined as any AEs with onset or worsening on or after date of first dose of study intervention through the day of last dose in sub-study. |
Countries
United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Study consisted of main study (12 treatment cycles) and sub study (single treatment cycle). Each cycle was of 28 days. Unique participants were enrolled either into main or sub-study. Study treatment was initiated between Day 29 and 90 post radical prostatectomy. After sub-study completion and serum testosterone assessment (primary analysis) and safety (secondary analysis), participants were transitioned into main study from Cycle 2 Day 1 and continued treatment through Cycle 12 in main study.
Participants by arm
| Arm | Count |
|---|---|
| Main Study: Apalutamide Plus Androgen Deprivation Therapy (ADT) In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT intramuscular or subcutaneous injection from Cycle 1 Day 1 up to Cycle 12. Each cycle was of 28 days. | 96 |
| Sub Study: Relugolix Followed by Apalutamide Plus Relugolix In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and accompanied by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide with ADT (oral relugolix) through Cycle 12. Each cycle was of 28 days. | 12 |
| Total | 108 |
Baseline characteristics
| Characteristic | Main Study: Apalutamide Plus Androgen Deprivation Therapy (ADT) | Total | Sub Study: Relugolix Followed by Apalutamide Plus Relugolix |
|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 7.33 | 65.2 years STANDARD_DEVIATION 7.42 | 64.6 years STANDARD_DEVIATION 8.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 99 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 15 Participants | 2 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 88 Participants | 8 Participants |
| Region of Enrollment UNITED STATES | 96 Participants | 108 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 96 Participants | 108 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 12 |
| other Total, other adverse events | 107 / 108 | 8 / 12 |
| serious Total, serious adverse events | 16 / 108 | 0 / 12 |
Outcome results
Primary
Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 24
Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed prostate specific antigen (PSA) greater than (\>) 0.2 nanogram per milliliter (ng/mL). Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study.
Time frame: At Month 24
Population: Modified intent-to-treat (MITT) analysis set included all participants who were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline prostate-specific antigen (PSA) and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 24 | 100 Percentage of participants |
Primary
Sub-study: Percentage of Participants Who Maintained Testosterone Level Less Than (<) 50 Nanograms Per Deciliter (ng/dL) Through Day 28
Percentage of participants maintaining testosterone level \<50 ng/dL through Day 28 were reported.
Time frame: From Day -14 through Day 28
Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for main study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Sub-study: Percentage of Participants Who Maintained Testosterone Level Less Than (<) 50 Nanograms Per Deciliter (ng/dL) Through Day 28 | 100 Percentage of participants |
Secondary
Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 12
Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed PSA \>0.2 ng/mL. Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study.
Time frame: At Month 12
Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 12 | 100 Percentage of participants |
Secondary
Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24
Percentage of participants with serum testosterone recovery (\>=150 ng/dL) at Months 18 and 24 were reported. Testosterone recovery was defined as a serum testosterone level greater than or equal to (\>=)150 nanograms per deciliter (ng/dL).
Time frame: At Months 18 and 24
Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24 | Month 18 | 42.0 Percentage of participants |
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24 | Month 24 | 77.4 Percentage of participants |
Secondary
Sub-study: Number of Participants With Treatment-emergent Adverse Events
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and it does not necessarily have a causal relationship with the intervention. TEAEs were defined as any AEs with onset or worsening on or after date of first dose of study intervention through the day of last dose in sub-study.
Time frame: From 1st dose of study intervention (relugolix on Day -14) up to end of sub-study (Day 28)
Population: Safety analysis set included all participants who received at least 1 dose of apalutamide. Data for this outcome measure was not planned to be collected and analyzed for main study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) | Sub-study: Number of Participants With Treatment-emergent Adverse Events | 8 Participants |