The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation

NCT05167175 | Unknown Phase 2 DMC

• 1 other identifier: PROact
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, prospective study to assess the efficacy and safety of Olaparib combined with Abiraterone plus Prednisone in subjects with metastatic hormone sensitive prostate cancer (mHSPC) who carry deleterious germline or homologous recombination repair (HRR) mutations. Olaparib is an oral, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor that potently inhibits the activity of deoxyribonucleic acid repair polymerases. Abiraterone acetate (AA) is a prodrug of abiraterone that potently inhibits cytochrome P450c17, a key enzyme in androgen biosynthesis. A total of 30 mHSPC subjects with HRR gene mutations that meet the criteria will be included in the study. Eligible subjects will receive oral Olaparib tablets 300 mg BID, combined with Abiraterone acetate 1000 mg QD plus Prednisone 5 mg, and the study will end when the primary endpoint radiographic progression-free survival (rPFS) data maturity reaches 60%. During the treatment and follow-up periods, all subjects will have regular visits to assess the efficacy and safety of Olaparib in combination with abiraterone acetate plus prednisone. Radiographic progression-free survival (rPFS), prostate-specific antigen response (PSA response rate), prostate-specific antigen progression-free survival (PSA-PFS), radiological objective response rate (ORR) and other indicators will be assessed and calculated.

Conditions

Prostate Cancer; Prostate Carcinoma; Metastatic Prostate Cancer

Keywords

HRR; Olaparib; mCSPC

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-Free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

  Time from the start of study drug to radiographic progression, or death due to any cause, whichever occurs first.

  18 month

Secondary Outcomes (3)

• PSA response rate

  18 month

• PSA Progression Free Survival (PSA-PFS) by Investigator

  18 month

• Confirmed Objective Response Rate (ORR) by Investigator

  18 month

Other Outcomes (1)

• Number of Participants Who Experience an Adverse Event (AE)

  18 month

Study Arms (1)

Intervention/Treatment

EXPERIMENTAL

Subjects will receive a regimen of Olaparib tablets 300 mg twice daily in combination with Abiraterone acetate 1000 mg plus Prednisone 5mg once daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).

Drug: Olaparib tablet; Drug: Abiraterone acetate; Drug: Prednisone tablet

Interventions

Olaparib tablet DRUG

Lynparza (Olaparib tablets) 300 mg should be taken orally twice daily.

Also known as: Lynparza

Intervention/Treatment

Abiraterone acetate DRUG

Qingkeshu (Abiraterone acetate tablets) 1000 mg should be taken orally once daily.

Also known as: Qingkeshu

Intervention/Treatment

Prednisone tablet DRUG

Prednisone Tablets should be taken 5 mg once daily.

Intervention/Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Adult male patients (age≥18 years old).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically confirmed adenocarcinoma of the prostate.
• Subjects must have at least 1 qualifying HRR gene mutation in tumor tissue by central lab (Glorious Med, shanghai, China).
• Archival or new biopsies are acceptable.
• Qualifying HRR gene mutations (deleterious or suspected deleterious gene alterations) are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51D and RAD54L mutations confirmed by the central lab.
• The subject had a serum testosterone level ≤ 50 ng/dL (≤ 1.75 nmol/L) before enrollment.
• Patients who have not undergone previous surgery must be taking and voluntarily continue taking LHRH analogues (agonists or antagonists) throughout the study treatment period.
• Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL without previous transfusion within 28 days.
• Absolute neutrophil count ≥ 1.5 × 10\^9/L.
• Platelet count ≥ 100 × 10\^9/L.
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) specified.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase) ≤ 2.5 × the specified ULN, unless liver metastases are present, in which case it must be ≤ 5 × ULN.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) .
• Previous enrolment in the present study.
• Subjects participated in another clinical study with a drug or plan to participate in another interventional clinical study within 30 days prior to enrollment.
• Prior treatment with any PARP inhibitor or any new hormone agent, including Olaparib, Niraparib, Abiraterone, Enzalutamide, Apalutamide, etc.
• Prior chemotherapy with any DNA-damaging cytotoxic agent unless used to treat non-prostate cancer and the last dose was at least 5 years prior to enrollment in this study. For example: Patients previously treated with mitoxantrone or platinum-based chemotherapy for prostate cancer are excluded.
• Patients who have received prior chemotherapy with any taxane. For example, patients who have received prior Docetaxel for prostate cancer are excluded.
• Other malignancies within the last 5 years.
• History of adrenal dysfunction.
• Presence of persistent uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg). Subjects with a history of hypertension are allowed to participate if blood pressure could be controlled within these limits by antihypertensive therapy.
• Uncontrolled or underlying cardiac disease on resting electrocardiogram (eg, but not limited to: unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QT prolongation \> 500 ms with Fridericia correction, congenital long QT syndrome).
• The subject had received any systemic anticancer therapy (except radiotherapy for palliative reasons) 3 weeks prior to study treatment.
• Treatment of bone metastases with denosumab or bisphosphonates such as zoledronic acid is allowed.
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, ritonavir, cobicistat, boceprevir or carbidetex-boosted protease inhibitors, indinavir, saquinavir, nelfinavir, baprevir, teicoplanavir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, sulfadiazine, fluconazole, diltiazem, vilapamil) requires a 2-week washout period prior to initiation of Olaparib therapy.
• Concomitant use of strong CYP3A inducers (e.g. phenobarbital, empagliflozin, enzalutamide, phenytoin, rifampin, rifapentine, rifabutin, carbamazepine, nevirapine, and Forsythia leaf) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). If co-administered with phenobarbital or enzalutamide, a 5-week washout period is required before the start of Olaparib therapy and a 3-week washout period is required when co-administered with other drugs.
• Subjects with major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• Hongqian Guo: lead
• AstraZeneca: collaborator
• Nanjing Chia-tai Tianqing Pharmaceutical: collaborator

Study Sites (1)

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University

Nanjing, Jiangsu, 210008, China

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Urology Department

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: December 22, 2021
• Study Start: March 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 25, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)