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

Neoadjuvant Therapy Clinical Trial

Official title:

A Prospective, Multi-arm, Multi-center Clinical Trial on Neoadjuvant Intense Endocrine Therapy for High Risk and Locally Advanced Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05406999
• Other study ID #: IUNU-PC-118
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2020
• Est. completion date: June 30, 2030

Study information

• Verified date: August 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: June 30, 2030
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• High Risk Prostate Cancer
• Locally Advanced Prostate Cancer
• Neoadjuvant Therapy
• Prostatic Neoplasms

Intervention

Drug:
• ADT
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.
• Abiraterone Acetate
1000 mg (250 mg×4 tablets) once daily, orally
• Prednisolone tablets
5 mg once daily, orally.
• Enzalutamide
160 mg (40 mg× 4 tablets) once daily, orally.
• Apalutamide
240 mg (60 mg×4 tablets) once daily, orally.
• Darotamide
600 mg (300 mg × 2 tablets) twice daily, orally.
• Rezvilutamide
240 mg (80 mg × 3 tablets) once daily orally
• PARP inhibitor
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.

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

Locations

Country	Name	City	State
China	Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic response rate	Pathologic response rate= Pathologic Complete Response (pCR) Rate + Minimal Residual Disease (MRD) rate	up to 3 years
Primary	3 year biochemical progression free survival (bPFS)	Biochemical progression free survival (bPFS) within 3 years	up to 3 years
Secondary	Metastasis-Free Survival (MFS)	Metastasis-Free Survival (MFS) after intense neoadjuvant therapy	up to 5 years
Secondary	Time to castration-resistant prostate cancer(CRPC)	Time to castration-resistant prostate cancer(CRPC) after intense neoadjuvant therapy	up to 5 years
Secondary	PSA response rate	Prostate specific antigen (PSA) drops = 98% after intense neoadjuvant therapy	up to 3 years
Secondary	Positive margin rate	The positive margin rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy	up to 6 months
Secondary	Pathologic downgrade rate	The pathologic downgrade rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy compared with initial T stage.	up to 6 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. All grades of adverse events will be documented.	up to 5 years