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

Nanjing University

Status and phase: Enrolling; Phase 2

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

Treatments: Procedure: Robot-assisted radical prostatectomy; Drug: Enzalutamide; Drug: Apalutamide; Drug: Abiraterone Acetate; Drug: ADT; Drug: Rezvilutamide; Drug: PARP inhibitor; Drug: Darotamide; Drug: Prednisolone tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT05406999

IUNU-PC-118

Details and patient eligibility

About

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.

Full 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.

Enrollment: 900 estimated patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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900 participants in 8 patient groups

ADT alone + prostatectomy

Active Comparator group

Description:

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.

Treatment:

Procedure: Robot-assisted radical prostatectomy

Drug: ADT

ADT plus Abiraterone

Experimental group

Description:

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.

Treatment:

Procedure: Robot-assisted radical prostatectomy

Drug: Abiraterone Acetate

Drug: ADT

Drug: Prednisolone tablets

ADT plus Enzalutamide

Experimental group

Description:

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.

Treatment:

Procedure: Robot-assisted radical prostatectomy

Drug: Enzalutamide

Drug: ADT

ADT plus Apalutamide

Experimental group

Description:

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.

Treatment:

Procedure: Robot-assisted radical prostatectomy

Drug: ADT

Drug: Apalutamide

ADT plus Darotamide

Experimental group

Description:

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.

Treatment:

Procedure: Robot-assisted radical prostatectomy

Drug: Darotamide

Drug: ADT

ADT plus Rizvilutamide

Experimental group

Description:

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.

Treatment:

Drug: Rezvilutamide

Procedure: Robot-assisted radical prostatectomy

Drug: ADT

PARP inhibitor + abiraterone + ADT

Experimental group

Description:

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.

Treatment:

Drug: PARP inhibitor

Procedure: Robot-assisted radical prostatectomy

Drug: Abiraterone Acetate

Drug: ADT

Drug: Prednisolone tablets

PARP inhibitor + ADT

Experimental group

Description:

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.

Treatment:

Drug: PARP inhibitor

Procedure: Robot-assisted radical prostatectomy

Drug: ADT