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

Phase 2

Recruiting

• Conditions: Intense Endocrine Therapy; Neoadjuvant Therapy; High Risk Prostate Cancer; Locally Advanced Prostate Cancer
• Interventions: Drug: ADT; Drug: PARP inhibitor; Drug: Darotamide; Drug: Abiraterone Acetate; Drug: Enzalutamide; Drug: Apalutamide; Drug: Rezvilutamide; Procedure: Robot-assisted radical prostatectomy; Drug: Prednisolone tablets

• Registration Number: NCT05406999
• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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.

Detailed Description

The study was designed to evaluate the efficacy and safety of different forms of neoadjuvant intense androgen deprivation therapy (ADT) compared with ADT alone, followed by prostatectomy.

Study Timeline

• Study Start: 2020-02-01
• Study First Submitted: 2022-05-29
• Study First Submitted QC: 2022-06-04
• Study First Posted: 2022-06-07
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-12
• Last Update Posted: 2022-08-16
• Primary Completion: 2026-12-31
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 900

Inclusion Criteria

1. All patients must have been histologically diagnosed of prostate cancer and must be eligible for radical prostatectomy.
2. 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).
3. Eastern Cooperative Oncology Group (ECOG) physical condition score ≤ 1.
4. Patients must have adequate hematologic function, hepatic function, renal function and cardiac function.
5. 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.
6. Fertile patients must be willing to use highly effective contraception during the study period and within 120 days of the last dose of treatment.

Exclusion Criteria

1. Patients with neuroendocrine, small cell, or sarcoma-like pathologic features are not eligible.
2. 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.
3. Patients with clinical or radiological evidence of extra-regional lymph node metastases or bone metastases or visceral metastases (any M1) are not eligible.
4. Patients who have previously received androgen deprivation therapy (medical or surgical) or focal treatment, radiotherapy, chemotherapy for prostate cancer are not eligible.
5. Patients with severe or uncontrolled concurrent infections are not eligible.
6. 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.
7. Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
8. 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.
9. Patients with mental illness, mental disability or inability to give informed consent are not eligible.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ADT plus Apalutamide	Robot-assisted radical prostatectomy	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.
PARP inhibitor + ADT	PARP inhibitor	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.
ADT plus Abiraterone	Prednisolone tablets	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.
ADT plus Rizvilutamide	Robot-assisted radical prostatectomy	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.
ADT alone + prostatectomy	Robot-assisted radical prostatectomy	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.
ADT plus Apalutamide	ADT	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.
ADT plus Darotamide	Robot-assisted radical prostatectomy	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.
PARP inhibitor + abiraterone + ADT	Prednisolone tablets	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.
ADT plus Abiraterone	Robot-assisted radical prostatectomy	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.
ADT plus Enzalutamide	Robot-assisted radical prostatectomy	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.
ADT plus Enzalutamide	ADT	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.
ADT plus Darotamide	Darotamide	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.
PARP inhibitor + abiraterone + ADT	PARP inhibitor	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.
PARP inhibitor + abiraterone + ADT	Robot-assisted radical prostatectomy	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.
PARP inhibitor + ADT	Robot-assisted radical prostatectomy	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.
ADT plus Rizvilutamide	ADT	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.
PARP inhibitor + abiraterone + ADT	ADT	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.
ADT alone + prostatectomy	ADT	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.
ADT plus Abiraterone	ADT	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.
ADT plus Darotamide	ADT	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.
PARP inhibitor + ADT	ADT	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.
ADT plus Abiraterone	Abiraterone Acetate	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.
ADT plus Enzalutamide	Enzalutamide	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.
ADT plus Apalutamide	Apalutamide	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.
ADT plus Rizvilutamide	Rezvilutamide	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.
PARP inhibitor + abiraterone + ADT	Abiraterone Acetate	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.

Primary Outcome Measures

Name	Time	Method
3 year biochemical progression free survival (bPFS)	up to 3 years	Biochemical progression free survival (bPFS) within 3 years
Pathologic response rate	up to 3 years	Pathologic response rate= Pathologic Complete Response (pCR) Rate + Minimal Residual Disease (MRD) rate

Secondary Outcome Measures

Name	Time	Method
Metastasis-Free Survival (MFS)	up to 5 years	Metastasis-Free Survival (MFS) after intense neoadjuvant therapy
PSA response rate	up to 3 years	Prostate specific antigen (PSA) drops ≥ 98% after intense neoadjuvant therapy
Positive margin rate	up to 6 months	The positive margin rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy
Time to castration-resistant prostate cancer（CRPC)	up to 5 years	Time to castration-resistant prostate cancer（CRPC) after intense neoadjuvant therapy
Pathologic downgrade rate	up to 6 months	The pathologic downgrade rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy compared with initial T stage.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	up to 5 years	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. All grades of adverse events will be documented.

Trial Locations

Locations (1)

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University; 🇨🇳 Nanjing, Jiangsu, China