A Phase 3, Open-label, Randomized, Prospective Study of Apalutamide With Continued Versus Intermittent Androgen-Deprivation Therapy (ADT) Following PSA Response in Participants With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
Overview
- Phase
- Phase 3
- Intervention
- Apalutamide
- Conditions
- Metastatic Castrate-sensitive Prostate Cancer
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 420
- Locations
- 127
- Primary Endpoint
- Percent Change From Randomization in Severity of Adjusted Hot Flash Score at 18 Months
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
The purpose of the study is to determine if the intermittent use of androgen-deprivation therapy (ADT) in participants with metastatic castrate-sensitive prostate cancer (mCSPC) who reached a prostate-specific antigen (PSA) level < 0.2 nanograms/millilitres (ng/mL) after 6 months of treatment with apalutamide and ADT combination therapy provides non-inferior radiographic progression-free survival (rPFS) and a reduced burden of hot flashes measured as 18-month percent change in severity adjusted hot flash score.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate
- •For participants not undergoing Gender-affirming care: Metastatic prostate cancer disease documented by conventional imaging (example, computed tomography \[CT\], magnetic resonance imaging \[MRI\], or bone scan) and/or next-generation imaging \[NGI\] demonstrating greater than or equal (\>=) 2 distinct extraprostatic sites of metastasis
- •For participants undergoing Gender-affirming care: No evidence of metastasis by either conventional imaging (example, CT, MRI, or bone scan) and/or NGI is also acceptable
- •For participants not undergoing gender-affirming care: testosterone levels \> 50 (ng/dL) nanograms per deciliter at screening, except for those who may have received ADT prior to screening. Participants are allowed to have received up to 3 months of (ADT) androgen-deprivation therapy prior to enrollment
- •For participants undergoing Gender-affirming care: There is no testosterone level requirement for inclusion
- •Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or
- •Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (example, wheelchair-bound due to prior spinal cord injury) and not related to prostate cancer or associated therapy
- •A participant must agree not to plan to conceive a child while enrolled in this study or within 3 months after the last dose of study treatment
- •Must be able to take whole apalutamide tablets by swallowing alone or with another vehicle (example, applesauce)
- •Assigned male at birth, inclusive of all gender identities
Exclusion Criteria
- •History of seizure or known condition that has been determined to significantly predispose to seizure per investigator
- •Pelvic lymph nodes as only site of metastasis
- •Known allergies, hypersensitivity, or intolerance to excipients of apalutamide
- •Any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events
- •Gastrointestinal disorder affecting absorption
- •Participants who have undergone a bilateral orchiectomy with the exception of participants who completed this as part of their gender-affirming care or a result of a variation in physical sex development
Arms & Interventions
Arm A (Intermittent ADT Group)
Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and treated with apalutamide with intermittent ADT per protocol or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first.
Intervention: Apalutamide
Arm A (Intermittent ADT Group)
Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and treated with apalutamide with intermittent ADT per protocol or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first.
Intervention: Androgen-deprivation Therapy (ADT)
Arm B (Continuous ADT Group)
Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and continue to receive apalutamide plus ADT or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first.
Intervention: Apalutamide
Arm B (Continuous ADT Group)
Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and continue to receive apalutamide plus ADT or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first.
Intervention: Androgen-deprivation Therapy (ADT)
Outcomes
Primary Outcomes
Percent Change From Randomization in Severity of Adjusted Hot Flash Score at 18 Months
Time Frame: From randomization (Day 1 of Cycle 7) up to 18 months
Severity adjusted hot flash score will be calculated from the hot flash diary which will be daily filled by the participants.
Percentage of Participants With 18-Months Radiographic Progression-free Survival (rPFS)
Time Frame: From randomization (Day 1 of Cycle 7) up to 18 months
rPFS is defined as the duration from the date of randomization to the date of first documentation of confirmed radiographic progressive disease or death due to any cause, whichever occurs first. rPFS will be assessed by investigators using conventional imaging (computed tomography \[CT\]/magnetic resonance imaging \[MRI\] and 99mTc bone scans).
Secondary Outcomes
- Mean Percentage Changes From Randomization in Severity Adjusted Hot Flash Score and Hot Flash Frequency(From randomization (Day 1 of Cycle 7), up to 5 years)
- Second Progression-free Survival (PFS2)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Overall Survival (OS)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Prostate Cancer-specific Survival(From randomization (Day 1 Cycle 7) up to 5 years)
- Serum Prostate Specific Antigen (PSA) Evaluations(From randomization (Day 1 of Cycle 7) up to 5 years)
- Duration of Time on Androgen-deprivation Therapy (ADT)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Time to First ADT Restart(From randomization (Day 1 of Cycle 7) up to 5 years)
- Duration of Time with Testosterone Level Less than (<) 50 nanograms per millilitre (ng/mL)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Time to Recovery of Testosterone >50 nanogram per decilitre (ng/dL)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Time to Recovery of Testosterone Greater Than or Equal (>=) Screening Testosterone Level(From randomization (Day 1 of Cycle 7) up to 5 years)
- Time to Testosterone Recovery to Normal Range (>270 ng/dL)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Time to Metastatic Castration-resistant Prostate Cancer (mCRPC)(From randomization (Day 1 of Cycle 7) up to 5 years)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Initial Treatment Phase: From Day 1 of Cycle 1 (each cycle 28 days) up to end of Cycle 6 (6 month); Main Treatment Phase: Day 1 of Cycle 7 up to end of study (up to 5 years))
- Number of Participants with Abnormal Clinical Laboratory Parameters(From Cycle 1 Day 1 up to 5 years)
- Number of Participants with Abnormal Vital Sign Parameters(From Cycle 1 Day 1 up to 5 years)
- Number of Participants with Abnormal Physical Examination Parameters(From Cycle 1 Day 1 up to 5 years)
- Hot Flash Related Daily Interference Score (HFRDIS)(Up to 5 years)
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score(Baseline up to 5 years)
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire -Prostate Cancer Module (EORTC-PR25) Questionnaire(Baseline up to 5 years)
- Change From Baseline in European Organization for the Research and Treatment of Cancer (EORTC) Customized Study Form(Baseline up to 5 years)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-Cog) Questionnaire(Baseline up to 5 years)
- Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Questionnaire(Baseline up to 5 years)
- Change From Baseline in Patient Health Questionnaire (PHQ-9) Questionnaire(Baseline up to 5 years)
- Change From Baseline in Patient Global Impression of Severity scale (PGIS) Questionnaire(Baseline up to 5 years)
- Change From Baseline in Patient Global Impression of Change (PGIC) Questionnaire(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by EORTC-QLQ-C30(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by EORTC-PR25(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by EORTC Customized Study Form(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by MAX-PC(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by PHQ-9(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by PGIS(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by PGIC(Baseline up to 5 years)
- Time to Recovery From Baseline as Assessed by PROMIS-Cog(Baseline up to 5 years)
- Time to Deterioration in EORTC-QLQ-C30 Over Time(Up to 5 years)
- Time to Deterioration in EORTC-PR25 Over Time(Up to 5 years)
- Time to Deterioration in EORTC Customized Study Form Over Time(Up to 5 years)
- Time to Deterioration as per PROMIS-Cog Questionnaire Over Time(Up to 5 years)
- Time to Deterioration in MAX-PC Questionnaire Over Time(Up to 5 years)
- Time to Deterioration as per PHQ-9 Questionnaire Over Time(Up to 5 years)
- Time to Deterioration in PGIS Questionnaire Over Time(Up to 5 years)
- Time to Deterioration as per PGIC Questionnaire Over Time(Up to 5 years)