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

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

To evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-sensitive Prostate Cancer
• Intervention / Treatment: Drug: Apalutamide

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
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hiroshi Yoshida; Phone Number: +81-3-3830-1074; Email: ctDNA@a2healthcare.com

Study Locations

• Japan
  • Osaka
    • Ōsaka-sayama, Osaka, Japan, 589-851
      • Recruiting
      • Kindai University Hospital
      • Contact: Hirotsugu Uemura, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Apalutamide; Apalutamide 240 mg administered orally once a day as four 60 mg tablets	Drug: Apalutamide; Apalutamide 240 mg administered orally once a day as four 60 mg tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kindai University
• Collaborators: Janssen Pharmaceutical K.K.
• Investigators: Study Chair: Hirotsugu Uemura, MD, PhD, Department of Urology, Kindai University Faculty of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2020
• Primary Completion (Anticipated): March 31, 2025
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Hypersensitivity; Prostatic Neoplasms
• Other Study ID Numbers: 56021927PCR4013 (Other Grant/Funding Number: Janssen Pharmaceutical K.K.); jRCTs071200040 (Registry Identifier: Japan Registry of Clinical Trial (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No