Study to Evaluate ctDNA of mCSPC Patients Receiving Apalutamide in Japan (CUARTET)

• ClinicalTrials.gov Identifier: NCT04601441
• Recruitment Status: Recruiting
• First Posted: October 23, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Kindai University
• Collaborator: Janssen Pharmaceutical K.K.
• Information provided by (Responsible Party): Hirotsugu Uemura, Kindai University

Tracking Information

• First Submitted Date: October 12, 2020
• First Posted Date: October 23, 2020
• Last Update Posted Date: December 8, 2020
• Actual Study Start Date: November 6, 2020
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2020)

Changes in genomic alterations of 73 PC driver genes between pre- and posttreatment of apalutamide. [ Time Frame: Three years or more, 4.5 years or less ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 23, 2020)

• The proportion of participants who achieve nadir PSA ≤0.2 ng/mL stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PSA-PFS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PFS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• OS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  The OS is defined as the duration from apalutamide initiation to any death.
• Time to CRPC stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PFS2 stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• Safety in the usual clinical practice based on adverse events [ Time Frame: From apalutamide initiation to 30 days after the last dose ]
  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.
• Safety in the usual clinical practice based on potential skin rash events [ Time Frame: From apalutamide initiation to 30 days after the last dose ]
  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.

Original Secondary Outcome Measures (submitted: October 19, 2020)

• The proportion of participants who achieve nadir PSA ≤0.2 ng/mL stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PSA-PFS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PFS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• OS stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  The OS is defined as the duration from apalutamide initiation to any death.
• Time to CRPC stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• PFS2 stratified by baseline genomic alterations for 73 PC driver genes [ Time Frame: Three years or more, 4.5 years or less ]
  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.
• Safety in the usual clinical practice based on adverse events [ Time Frame: From apalutamide initiation to 30 days after the last dose ]
  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.
• Safety in the usual clinical practice based on potential skin rash events [ Time Frame: From apalutamide initiation to 30 days after the last dose ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate ctDNA of mCSPC Patients Receiving Apalutamide in Japan
• Official Title: Phase 4 Study of Exploring Circulating Tumor DNA (ctDNA) of Metastatic Castration-sensitive Prostate Cancer (mCSPC) Patients Receiving Apalutamide in Japan
• Brief Summary: To evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Screening
• Condition: Metastatic Castration-sensitive Prostate Cancer

Intervention

Drug: Apalutamide

Apalutamide 240 mg administered orally once a day as four 60 mg tablets

Study Arms

Apalutamide

Apalutamide 240 mg administered orally once a day as four 60 mg tablets

Intervention: Drug: Apalutamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 19, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2025
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Hiroshi Yoshida; +81-3-3830-1074; ctDNA@a2healthcare.com

• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04601441
• Other Study ID Numbers: 56021927PCR4013; jRCTs071200040 ( Registry Identifier: Japan Registry of Clinical Trial (jRCT) ); 56021927PCR4013 ( Other Grant/Funding Number: Janssen Pharmaceutical K.K. )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hirotsugu Uemura, Kindai University
• Original Responsible Party: Same as current
• Current Study Sponsor: Kindai University
• Original Study Sponsor: Same as current
• Collaborators: Janssen Pharmaceutical K.K.

Investigators

• Study Chair: Hirotsugu Uemura, MD, PhD; Department of Urology, Kindai University Faculty of Medicine

• PRS Account: Kindai University
• Verification Date: December 2020