Neoadjuvant Therapy of Darolutamide Plus ADT for High Risk Prostate Cancer

Neoadjuvant ADT +/- Darolutamide Followed by Radical Prostatectomy for High-risk Prostate Cancer: a Randomized, Open Label Trial

The purpose of this study is to determine if treatment with Darolutamide plus androgen deprivation therapy (ADT) before radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and pathological tumor volume with minimal residual disease (MRD)) as compared to ADT.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide; Drug: Goserelin 3.6 mg

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weijun Qin, MD; Phone Number: 029-84771579; Email: qinwj@fmmu.edu.cn
• Study Contact Backup: Name: Jingliang Zhang, MD; Email: zhangjingliang@fmmu.edu.cn

Study Locations

• China
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Recruiting
      • The First Affillated Hospital, the Air Force Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be ≥ 18 and ≤75 years of age.
• All patients must have a histologically or cytologically diagnosis of prostate cancer and must be eligible for radical prostatectomy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤1.
• All patients must complete mpMRI or 68Ga-PSMA PET / CT before and after neoadjuvant treatment.
• All patients must undergo thorough tumor staging and meet one of the following criteria: 1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ cT2c or cN+or locally advanced, 2. Gleason score of primary tumor ≥ 8, 3. prostate specific antigen (PSA) ≥20 ng/ml.
• Patients must have adequate organ function as defined by the following criteria(within 28 days prior to registration):

white blood cell (WBC) ≥ 4.0 × 109 / L platelets≥ 100 × 109 / L hemoglobin ≥ 9 g / dL international normalized ratio (INR) < 1.5. total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN) SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN serum creatinine ≤2×ULN

• 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 be willing to obey the prohibitions and restrictions specified in the research protocol.

Exclusion Criteria:

• clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases.
• Prior androgen deprivation therapy (medical or surgical) or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy.
• severe or uncontrolled concurrent infections.
• New York Heart Association Class III or IV congestive heart failure at the time of screening.
• uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
• Patients with mental illness, mental disability or inability to give informed consent are not eligible.
• Patients 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide Plus ADT; All participants in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus Darolutamide. Goserelin 3.6 mg will be used once per 4 weeks. Darolutamide will be administered orally as 600 mg twice a day. Subjects will continue to take Darolutamide Plus Goserelin for 12 weeks before radical prostatectomy	Drug: Darolutamide; 600 mg orally twice daily for 12 weeks before radical prostatectomy; Drug: Goserelin 3.6 mg; 3.6 mg goserelin hypodermic once per 4 weeks
Experimental: ADT alone; All participants in this arm will receive LHRHa alone for 12 weeks before receiving radical prostatectomy. Goserelin 3.6 mg will be administered once per 4 weeks.	Drug: Goserelin 3.6 mg; 3.6 mg goserelin hypodermic once per 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate	The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy	After 12 weeks of neoadjuvant therapy + RP + PLND
Proportion of Subjects With Minimal Residual Disease	The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy	After 12 weeks of neoadjuvant therapy + RP + PLND

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Stage Degradation	Clinical or pathological stage degradation after neoadjuvant therapy	After 12 weeks of neoadjuvant therapy + RP + PLND
Rate of Positive Surgical Margins	The proportion of subjects with positive surgical margins after radical prostatectomy	After 12 weeks of neoadjuvant therapy + RP + PLND
Rate of Complete Serum Remission	The proportion of subjects whose PSA is less than or equal to 0.2 ng/ml after 3 months of treatment	After 12 weeks of neoadjuvant therapy
Proportion of subjects without PSA progression	The proportion of subjects whose PSA has never gone below 1 ng/ml or who receive any radiotherapy or systemic treatment after radical prostatectomy	2 years after RP
Imaging Response Rate	The proportion of subjects whose primary tumor is in complete remission on imaging or residual tumor's maximum diameter is less than 0.5cm	After 12 weeks of neoadjuvant therapy
Recovery time of urinary continence (day)	The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day.	1 years after RP
biochemical recurrence-free survival (bRFS)	biochemical recurrence-free survival (bRFS) defined as time to PSA ≥ 0.2 ng/ml after radical prostatectomy.	3 years after RP
metastasis-free survival (MFS)	time from date of randomization to date of evidence of systemic disease on bone scan or cross-sectional imaging.	5 years after RP

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Weijun Qin, MD, The First Affillated Hospital, the Air Force Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Goserelin
• Other Study ID Numbers: KY20242118-C-1

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