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

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05406999
• Collaborator: (none)
• Enrollment: 900
• Location: 1
• Arms: 8
• Anticipated Duration (Months): 124.9
• Patients Per Site Per Month: 7.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoadjuvant Therapy; High Risk Prostate Cancer; Locally Advanced Prostate Cancer; Intense Endocrine Therapy	Drug: ADT; Drug: Abiraterone Acetate; Drug: Prednisolone tablets; Drug: Enzalutamide; Drug: Apalutamide; Drug: Darotamide; Drug: Rezvilutamide; Drug: PARP inhibitor; Procedure: Robot-assisted radical prostatectomy	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 900 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-arm, Multi-center Clinical Trial on Neoadjuvant Intense Endocrine Therapy for High Risk and Locally Advanced Prostate Cancer
• Actual Study Start Date: Feb 1, 2020
• Anticipated Primary Completion Date: Dec 31, 2026
• Anticipated Study Completion Date: Jun 30, 2030

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ADT alone + 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.	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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: ADT plus Abiraterone 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; 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.; Drug: Abiraterone Acetate; 1000 mg (250 mg×4 tablets) once daily, orally; Drug: Prednisolone tablets; 5 mg once daily, orally.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: ADT plus 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.	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.; Drug: Enzalutamide; 160 mg (40 mg× 4 tablets) once daily, orally.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: ADT plus 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.	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.; Drug: Apalutamide; 240 mg (60 mg×4 tablets) once daily, orally.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: ADT plus 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.	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.; Drug: Darotamide; 600 mg (300 mg × 2 tablets) twice daily, orally.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: ADT plus Rizvilutamide 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; 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.; Drug: Rezvilutamide; 240 mg (80 mg × 3 tablets) once daily orally; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.
Experimental: PARP inhibitor + abiraterone + 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.	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.; Drug: Abiraterone Acetate; 1000 mg (250 mg×4 tablets) once daily, orally; Drug: Prednisolone tablets; 5 mg once daily, orally.; Drug: 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.
Experimental: PARP inhibitor + 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.	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.; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Pathologic response rate [up to 3 years]

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

2. 3 year biochemical progression free survival (bPFS) [up to 3 years]

   Biochemical progression free survival (bPFS) within 3 years

Secondary Outcome Measures

1. Metastasis-Free Survival (MFS) [up to 5 years]

   Metastasis-Free Survival (MFS) after intense neoadjuvant therapy

2. Time to castration-resistant prostate cancer（CRPC) [up to 5 years]

   Time to castration-resistant prostate cancer（CRPC) after intense neoadjuvant therapy

3. PSA response rate [up to 3 years]

   Prostate specific antigen (PSA) drops ≥ 98% after intense neoadjuvant therapy

4. Positive margin rate [up to 6 months]

   The positive margin rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University	Nanjing	Jiangsu	China	210000

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hongqian Guo, Chief Physician, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• ClinicalTrials.gov Identifier: NCT05406999
• Other Study ID Numbers: IUNU-PC-118
• First Posted: Jun 7, 2022
• Last Update Posted: Aug 16, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisolone; Abiraterone Acetate; Poly(ADP-ribose) Polymerase Inhibitors

Study Results

No Results Posted as of Aug 16, 2022