Fluzoparib and Abiraterone in the preSurgery Treatment of Prostate Cancer: FAST Trial

NCT05223582 | Unknown Phase 2

• 1 other identifier: FAST trial
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the safety and efficacy of fluzoparib combined with abiraterone in neoadjuvant treatment of patients with high-risk locoregional prostate cancer. Dr. Yao Zhu from Fudan University Shanghai Cancer Center is the co-leading PI of this study.

Conditions

High-risk Prostate Cancer; Neoadjuvant Therapy

Keywords

Prostate cancer; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) or minimal residual disease (MRD) rate

  Pathological response, defined as achieving either pCR or MRD at radical prostatectomy (RP). pCR is defined as the absence of morphologically identifiable carcinoma in the RP specimen. MRD will be defined as residual tumor in the RP specimen measuring ≤ 5 mm.

  1 month after prostatectomy as local treatment for primary lesion

Secondary Outcomes (7)

• Biochemical progression-free survival

  Up to 2 years

• Metastasis-free survival

  Up to 2 years

• PSA responses

  During the treatment

• surgical margins

  1 month after prostatectomy as local treatment for primary lesion

• pathological stage

  1 month after prostatectomy as local treatment for primary lesion

Other Outcomes (1)

• Prespecified and exploratory biomarkers

  after prostatectomy as local treatment for primary lesion

Study Arms (1)

Fluzoparib and abiraterone treatment group

EXPERIMENTAL

Patients would be treated with 1000mg abiraterone qd. Patients would be treated with 150mg fluzoparib bid. Patients would be treated with 5mg prednisone bid. Patients would get medical castration.

Drug: Abiraterone acetate; Drug: Fluzoparib; Drug: Prednisone; Drug: Androgen deprivation therapy; Procedure: Radical Prostatectomy

Interventions

Abiraterone acetate DRUG

Patients would be treated with 1000mg abiraterone qd.

Fluzoparib and abiraterone treatment group

Fluzoparib DRUG

Patients would be treated with 150mg fluzoparib bid.

Fluzoparib and abiraterone treatment group

Prednisone DRUG

Patients would be treated with 5mg prednisone bid.

Fluzoparib and abiraterone treatment group

Androgen deprivation therapy DRUG

Patients would get medical castration.

Fluzoparib and abiraterone treatment group

Radical Prostatectomy PROCEDURE

Patients would get radical prostatectomy after the neoadjuvant treatment.

Fluzoparib and abiraterone treatment group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Patients must have histologically or cytologically confirmed prostate adenocarcinoma, clinically assessed as localized or with only pelvic lymph node metastasis according to radiological evaluation, and categorized as high- or very-high risk per the National Comprehensive Cancer Network (NCCN) guidelines.
• Patients need to maintain effective luteinizing hormone-releasing hormone analogue (LHRHa) therapy throughout the study treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
• Males choosing radical prostatectomy as the primary treatment for prostate cancer.
• Normal bone marrow function: Absolute neutrophil count ≥ 1.5×10\^9/L; platelets ≥ 100×10\^9/L; hemoglobin ≥ 90g/L; white blood cell count ≥ 3.6×10\^9/L.
• Normal liver function: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 ULN (upper limit of normal), total bilirubin ≤ 1.5 times ULN, Child-Pugh Class A, serum albumin ≥ 3g/dL.
• Normal coagulation function: International normalized ratio (INR) ≤ 1.5, activated partial thromboplastin time (APTT) ≤ 1.5 ULN, prothrombin time (PT) \< ULN + 4 seconds.
• Normal cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; QTc \< 450ms for males, \< 470ms for females, blood potassium ≥ 3.5mmol/L.
• Normal blood pressure: Systolic blood pressure \< 160mmHg, diastolic blood pressure \< 95mmHg, patients with normal blood pressure after appropriate clinical treatment can be included.
• Normal kidney function: Serum creatinine ≤ 1.5 ULN, creatinine clearance ≥ 50 mL/min.
• Patients deemed to have the ability to ejaculate and an active sexual life must agree to use effective contraception and not to donate sperm from the first administration of the study drug until 3 months after the last administration.
• Patients are able to understand and willing to sign the informed consent form. Patients are able to comply with the study visit schedule and other protocol requirements.

You may not qualify if:

• Patients with a history of other malignant tumors, myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or who have had other malignant tumors within 5 years before the first dosa (excluding completely resolved in situ cancers and malignancies deemed by the investigator to progress slowly).
• Patients who have undergone local treatment for prostate cancer (such as radical prostatectomy, radiotherapy, or brachytherapy).
• Patients who have received radiotherapy or major surgery within 3 weeks before the first dose or participated in another drug clinical trial within 4 weeks before the first dose.
• Patients planning to receive any other antitumor therapy during the study treatment.
• Patients who have received treatment with PARP inhibitors (e.g., fluzoparib, olaparib, talazoparib, veliparib, niraparib, lucaparib, or others), chemotherapy (e.g., docetaxel, cisplatin, carboplatin, oxaliplatin, or others), mitoxantrone, cyclophosphamide, CYP17 inhibitors such as ketoconazole, conventional anti-androgen therapy (luteinizing hormone-releasing hormone \[LHRH\] agonists/antagonists, bicalutamide, nilutamide), novel hormonal therapy (e.g., abiraterone, enzalutamide, apalutamide), or immunotherapy (e.g., sipuleucel-T vaccine, ipilimumab). Patients who have received conventional anti-androgen therapy or abiraterone for no more than 1 month are allowed to enroll.
• Patients who have previous treated with strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, ritonavir, cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The washout period before the first dose should be at least 2 weeks.
• Patients who have previous treated with strong CYP3A inducers (e.g., phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, carbamazepine, nevirapine) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The washout period before the first dose should be at least 5 weeks for phenobarbital or enzalutamide and 3 weeks for other drugs.
• Habitual drinking grapefruit juice or excessive tea, coffee, and/or caffeine-containing beverages, which cannot be discontinued during the study.
• Inability to discontinue the use of medications that may affect P-glycoprotein (P-gp) during the study, including but not limited to amiodarone, carvedilol, clarithromycin, delavirdine, erythromycin, lapatinib, lopinavir, nelfinavir, propranolol, quinidine, ranolazine, tipranavir, and verapamil.
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases, active or symptomatic viral hepatitis, or chronic liver disease (HBV viral load ≥ 10\^4 copies/mL, HCV viral load ≥ 10\^3 copies/mL).
• Clinically significant heart disease, such as New York Heart Association (NYHA) Class III-IV heart failure, myocardial infarction within the past 6 months, severe or unstable angina, or recent ventricular arrhythmias.
• Preexisting duodenal stents or any gastrointestinal disorder or defect that the investigator believes would interfere with drug absorption.
• Habitual constipation or diarrhea, irritable bowel syndrome, or inflammatory bowel disease; intra-abdominal fistula, gastrointestinal perforation, or abdominal abscess within the past 6 months, requiring blood transfusion for gastrointestinal bleeding.
• Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors affecting medication intake and absorption.
• History of asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs) or classified as "mild persistent" or more severe asthma history (symptoms ≥ 2 days per week).

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; fluzoparib; Prednisone; Androgen Antagonists

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; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 4, 2022
• Study Start: May 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Access Criteria: The IPD could be shared for scientific purposes by contacting the PI via email.

Locations

CN (1)