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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 900
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
      • Contact: Junlong Zhuang, MD; Phone Number: 8615950451917; Email: zhuangjl-2008@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / 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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; Drug: Abiraterone Acetate; 1000 mg (250 mg×4 tablets) once daily, orally; Drug: Prednisolone tablets; 5 mg once daily, orally.
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; Drug: Enzalutamide; 160 mg (40 mg× 4 tablets) once daily, orally.
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; Drug: Apalutamide; 240 mg (60 mg×4 tablets) once daily, orally.
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; Drug: Darotamide; 600 mg (300 mg × 2 tablets) twice daily, orally.
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; Drug: Rezvilutamide; 240 mg (80 mg × 3 tablets) once daily orally
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; 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.
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.; Procedure: Robot-assisted radical prostatectomy; Robot-assisted radical prostatectomy was performed within 2 weeks after the end of the therapy.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-Free Survival (MFS)	Metastasis-Free Survival (MFS) after intense neoadjuvant therapy	up to 5 years
Time to castration-resistant prostate cancer（CRPC)	Time to castration-resistant prostate cancer（CRPC) after intense neoadjuvant therapy	up to 5 years
PSA response rate	Prostate specific antigen (PSA) drops ≥ 98% after intense neoadjuvant therapy	up to 3 years
Positive margin rate	The positive margin rate of whole-mount pathology for prostatectomy after intense neoadjuvant therapy	up to 6 months
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): June 30, 2030

Study Registration Dates

• First Submitted: May 29, 2022
• First Submitted That Met QC Criteria: June 4, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisolone; Abiraterone Acetate; Poly(ADP-ribose) Polymerase Inhibitors
• Other Study ID Numbers: IUNU-PC-118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No