Study to Evaluate ctDNA of mCSPC Patients Receiving Apalutamide in Japan

Study Overview
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Brief Summary
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To evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment

Detailed Description
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This clinical study is an open-label, multicenter, interventional, Phase 4 study to evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment in patients with mCSPC. A total of 100 participants to be treated by apalutamide will be registered in this study. All participants will undergo blood collection for ctDNA, single-nucleotide polymorphisms (SNPs), and human-leukocyte antigen (HLA) typing at pre- and posttreatment of apalutamide.

Official Title
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Phase 4 Study of Exploring Circulating Tumor DNA (ctDNA) of Metastatic Castration-sensitive Prostate Cancer (mCSPC) Patients Receiving Apalutamide in Japan

Conditions
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Metastatic Castration-sensitive Prostate Cancer

Intervention / Treatment
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* Drug: Apalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged ≥20 years. Participant has documented diagnosis of metastatic PC with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology. Participant has metastatic PC that is castration naïve or castration sensitive and is permitted to receive less than 6-months ADT or CAB before registration and less than 36-months neoadjuvant or adjuvant hormonal therapy. If a participant is treated with ADT or CAB, he has maintained a response to hormonal therapy of stable disease or better, by investigator assessment of imaging and PSA. Participant is willing to receive apalutamide for mCSPC in the participating site of this study. Participant is of Japanese nationality. Participant must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. Exclusion Criteria: Participant does not agree to assess ctDNA including 73 PC driver genes, SNPs, and HLA typing. Participant has received any prior therapy of abiraterone, docetaxel, enzalutamide, apalutamide or darolutamide. Participant has known allergies, hypersensitivity, or intolerance to apalutamide or its excipients (refer to the package insert). Participant has contraindications to the use of ADT based on routine treatment. Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the evaluation of active double cancer, etc.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Apalutamide<br>Apalutamide 240 mg administered orally once a day as four 60 mg tablets | Drug: Apalutamide<br>* Apalutamide 240 mg administered orally once a day as four 60 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in genomic alterations of 73 PC driver genes between pre- and posttreatment of apalutamide. | Seventy-three PC driver genes from ctDNA including ARID1A, HSD3B1, MDM4, AKT3, MSH2, MSH6, ERCC3, NFE2L2, IDH1, FANCD2, MLH1, CTNNB1, FOXP1, RYBP, PIK3CB, ATR, PIK3CA, FBXW7, PIK3R1, CHD1, APC, FANCE, CDK6, MET, BRAF, CUL1, KMT2C, NKX3-1, CLU, NCOA2, MYC, CDKN2A, FANCG, FANCC, PTEN, FANCF, CCND1, ATM, ZBTB16, CDKN1B, KRAS, KMT2D, CDK4, MDM2, BRCA2, RB1, ERCC5, FOXA1, RAD51B, AKT1, IDH2, ERCC4, ZFHX3, FANCA, TP53, CDK12, BRCA1, SPOP, RNF43, RAD51C, AKT2, ERCC2, ERCC1, ASXL1, GNAS, RUNX1, ERG, TMPRSS2, KDM6A, AR, MED12, SMARCA1, and PALB2. | Three years or more, 4.5 years or less | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants who achieve nadir PSA ≤0.2 ng/mL stratified by baseline genomic alterations for 73 PC driver genes | The proportion of participants who achieve nadir PSA ≤0.2 ng/mL is defined as the proportion of participants who achieve nadir PSA less than 0.2 ng/mL from apalutamide initiation. | Three years or more, 4.5 years or less | 
| PSA-PFS stratified by baseline genomic alterations for 73 PC driver genes | The PSA-PFS is defined as the duration from apalutamide initiation to either PSA progression or death, whichever occurs first. The PSA progression will be determined according to the PCWG3 criteria. | Three years or more, 4.5 years or less | 
| PFS stratified by baseline genomic alterations for 73 PC driver genes | The PFS is defined as the duration from apalutamide initiation to either radiographic progression, clinical progression or death, whichever occurs first. The radiographic and clinical progression will be determined by an investigator's discretion. | Three years or more, 4.5 years or less | 
| OS stratified by baseline genomic alterations for 73 PC driver genes | The OS is defined as the duration from apalutamide initiation to any death. | Three years or more, 4.5 years or less | 
| Time to CRPC stratified by baseline genomic alterations for 73 PC driver genes | The time to CRPC is defined as the duration from apalutamide initiation to developing CRPC. The CRPC will be determined according to European Association of Urology (EAU) guidelines 2019. | Three years or more, 4.5 years or less | 
| PFS2 stratified by baseline genomic alterations for 73 PC driver genes | The PFS2 is defined as the duration from apalutamide initiation to disease progression (PSA progression, radiographic progression, or clinical progression) on the first subsequent therapy for prostate cancer, whichever occurred first. The PSA progression will be determined according to the PCWG3 criteria. The radiographic and clinical progression will be determined by an investigator's discretion. | Three years or more, 4.5 years or less | 
| Safety in the usual clinical practice based on adverse events | Safety observational period is defined as the treatment phase in this study. Adverse events that occur within 30 days after the last dose of apalutamide will be collected, except for lost to follow-up, death, or withdrawal of consent for study participation. For each adverse event, the percentage of participants who experience at least 1 occurrence of the given event will be summarized. | From apalutamide initiation to 30 days after the last dose | 
| Safety in the usual clinical practice based on potential skin rash events | Safety observational period is defined as the treatment phase in this study. Potential skin rash events that occur within 30 days after the last dose of apalutamide will be collected, except for lost to follow-up, death, or withdrawal of consent for study participation. The percentage of participants who experience at least 1 occurrence of the given event will be summarized. | From apalutamide initiation to 30 days after the last dose |