Neoadjuvant Intense Endocrine Therapy for High Risk and Locally Advanced Prostate Cancer

NCT05406999 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IUNU-PC-118
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, multi-arm, non-randomized, open-label clinical trial to evaluate the efficacy and safety of neoadjuvant intense endocrine therapy for high-risk or locally advanced prostate cancer.

Conditions

Neoadjuvant Therapy; High Risk Prostate Cancer; Locally Advanced Prostate Cancer; Intense Endocrine Therapy

Outcome Measures

Primary Outcomes (2)

• Pathologic response rate

  Pathologic response rate= Pathologic Complete Response (pCR) Rate + Minimal Residual Disease (MRD) rate

  up to 3 years

• 3 year biochemical progression free survival (bPFS)

  Biochemical progression free survival (bPFS) within 3 years

  up to 3 years

Secondary Outcomes (6)

• Metastasis-Free Survival (MFS)

  up to 5 years

• Time to castration-resistant prostate cancer（CRPC)

  up to 5 years

• PSA response rate

  up to 3 years

• Positive margin rate

  up to 6 months

• Pathologic downgrade rate

  up to 6 months

Study Arms (8)

ADT alone + prostatectomy

ACTIVE COMPARATOR

A total of 100 subjects receive ADT for 6 cycles (28 days per cycle) before prostatectomy. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Procedure: Robot-assisted radical prostatectomy

ADT plus Abiraterone

EXPERIMENTAL

A total of 150 subjects in this group received abiraterone acetate + prednisolone acetate daily for 6 cycles along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Abiraterone Acetate; Drug: Prednisolone tablets; Procedure: Robot-assisted radical prostatectomy

ADT plus Enzalutamide

EXPERIMENTAL

A total of 50 subjects in this group received enzalutamide daily for 6 cycles along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Enzalutamide; Procedure: Robot-assisted radical prostatectomy

ADT plus Apalutamide

EXPERIMENTAL

A total of 150 subjects in this group received apalutamide daily for 6 cycles along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Apalutamide; Procedure: Robot-assisted radical prostatectomy

ADT plus Darotamide

EXPERIMENTAL

A total of 150 subjects in this group received darotamide daily for 6 cycles along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Darotamide; Procedure: Robot-assisted radical prostatectomy

ADT plus Rizvilutamide

EXPERIMENTAL

A total of 150 subjects in this group received rizvilutamide daily for 6 cycles along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Rezvilutamide; Procedure: Robot-assisted radical prostatectomy

PARP inhibitor + abiraterone + ADT

EXPERIMENTAL

A total of 100 subjects in this group received Poly ADP-ribose Polymerase (PARP) Inhibitor plus abiraterone along with ADT. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: Abiraterone Acetate; Drug: Prednisolone tablets; Drug: PARP inhibitor; Procedure: Robot-assisted radical prostatectomy

PARP inhibitor + ADT

EXPERIMENTAL

A total of 50 subjects in this group in this group received Poly ADP-ribose Polymerase (PARP) Inhibitor along with ADT mentioned above. Enrolled patients carry homologous recombination repair (HRR) gene mutation verified by molecular testing. Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

Drug: ADT; Drug: PARP inhibitor; Procedure: Robot-assisted radical prostatectomy

Interventions

ADT DRUG

The ADT regimen will be determined by the investigators at separate centers. The dose and frequency of administration will be consistent with the prescribing information. Available drugs include triptorelin, goserelin, leuprolide, digareke ect.

ADT alone + prostatectomy; ADT plus Abiraterone; ADT plus Apalutamide; ADT plus Darotamide; ADT plus Enzalutamide; ADT plus Rizvilutamide; PARP inhibitor + ADT; PARP inhibitor + abiraterone + ADT

Abiraterone Acetate DRUG

1000 mg (250 mg×4 tablets) once daily, orally

ADT plus Abiraterone; PARP inhibitor + abiraterone + ADT

Prednisolone tablets DRUG

5 mg once daily, orally.

ADT plus Abiraterone; PARP inhibitor + abiraterone + ADT

Enzalutamide DRUG

160 mg (40 mg× 4 tablets) once daily, orally.

ADT plus Enzalutamide

Apalutamide DRUG

240 mg (60 mg×4 tablets) once daily, orally.

ADT plus Apalutamide

Darotamide DRUG

600 mg (300 mg × 2 tablets) twice daily, orally.

ADT plus Darotamide

Rezvilutamide DRUG

240 mg (80 mg × 3 tablets) once daily orally

ADT plus Rizvilutamide

PARP inhibitor DRUG

The PARP inhibitors will be determined by the investigators at separate centers. The dosage and frequency of administration will be consistent with the prescribing information. Available drugs include olaparib, fluzoparib, pamiparib, talazoparib ect.

PARP inhibitor + ADT; PARP inhibitor + abiraterone + ADT

Robot-assisted radical prostatectomy PROCEDURE

Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.

ADT alone + prostatectomy; ADT plus Abiraterone; ADT plus Apalutamide; ADT plus Darotamide; ADT plus Enzalutamide; ADT plus Rizvilutamide; PARP inhibitor + ADT; PARP inhibitor + abiraterone + ADT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have been histologically diagnosed of prostate cancer and must be eligible for radical prostatectomy.
• All patients must undergo thorough tumor staging and meet one of the following criteria: a) multi-parameter MRI or PSMA PET/CT shows clinical staging of primary tumor ≥ T3; b) Gleason score of primary tumor ≥ 8; c)prostate specific antigen(PSA) ≥20 ng/ml; d) Imaging evaluation shows regional lymph node metastases (N1).
• Eastern Cooperative Oncology Group (ECOG) physical condition score ≤ 1.
• Patients must have adequate hematologic function, hepatic function, renal function and cardiac function.
• Patients must participate voluntarily and sign an informed consent form(ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must bewilling to obey the prohibitions and restrictions specified in the research protocol.
• Fertile patients must be willing to use highly effective contraception during the study period and within 120 days of the last dose of treatment.

You may not qualify if:

• Patients with neuroendocrine, small cell, or sarcoma-like pathologic features are not eligible.
• Patients with low-risk or medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: a) multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor \< T3; b) Gleason score of primary tumor \< 8; c) prostate specific antigen (PSA) \<20 ng/ml.
• Patients with clinical or radiological evidence of extra-regional lymph node metastases or bone metastases or visceral metastases (any M1) are not eligible.
• Patients who have previously received androgen deprivation therapy (medical or surgical) or focal treatment, radiotherapy, chemotherapy for prostate cancer are not eligible.
• Patients with severe or uncontrolled concurrent infections are not eligible.
• Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration.
• Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
• Patients must not have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled.
• Patients with mental illness, mental disability or inability to give informed consent are not eligible.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

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

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Interventions

Abiraterone Acetate; Prednisolone; enzalutamide; apalutamide; Poly(ADP-ribose) Polymerase Inhibitors

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 29, 2022
• First Posted: June 7, 2022
• Study Start: February 1, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 16, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)