A Phase II Neoadjuvant Study of Darolutamide Plus ADT in Men With Localized Prostate Cancer

A Phase II, Multi-center, Single-arm, Prospective Study of Darolutamide + ADT Prior to Radical Prostatectomy (RP) in High-risk/Very High-risk Localized Prostate Cancer

Scientific Rationale: High risk localized prostate cancer (PCa) is associated with higher rates of biochemical recurrence, clinical recurrence, metastasis and PCa-specific death. Novel hormone therapies(NHT) have shown a significant survival advantage with respect to classical ADT in later stages of PCa and have already been investigated in neoadjuvant setting.

PURPOSE: To assess antitumor effect by measuring pathological tumor volume with pathological downstaging following radical prostatectomy + pelvic lymph-node dissection (RP + PLND) for high-risk localized prostate cancer patients.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide+ADT

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhisong He, MD; Phone Number: +8610-83572418; Email: wyj7074@sohu.com
• Study Contact Backup: Name: Kaiwei Yang, MD; Phone Number: 13811501435; Email: 13811501435@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University First Hospital
    • Contact: Zhisong He, MD; Phone Number: +8610-83572418; Email: wyj7074@sohu.com
    • Contact: Kaiwei Yang, MD; Phone Number: 13811501435; Email: 13811501435@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male ≥18 years of age.
2. Able to Sign informed consent form independently.
3. Non-metastatic adenocarcinoma of the prostate.
4. Subjects must have as least one of the following features according to NCCN definition of high-risk: Gleason score ≥8, or PSA >20ng/ml,or≥clinical T3a.
5. Subjects with pelvic lymph node involvement(N1) can be included.
6. Candidate for radical prostatectomy with or without pelvic lymph node dissection as per the investigator.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
8. Subjects must have normal organ and marrow function as defined below:

Hemoglobin ≥ 9.0 g/dL;Absolute neutrophil count (ANC) ≥ 1,500/mcL; Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start; Serum potassium ≥ 3.5 mmol/L; Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible);Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;Serum albumin ≥ 3.0 g/dL;Serum creatinine < 2.0 x ULN.

Exclusion Criteria:

1. Prostate cancer with neuroendocrine differentiation or small cell features
2. Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
3. History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer.
4. Subjects who are planning bilateral orchidectomy during the treatment period of the study.
5. Intolerable with darolutamide or ADT treatment.
6. Candidates of other clinical trials.
7. Any prior malignancy within 5 years.
8. Complications include significant cardiovascular disease, active infection, astrointestinal disorders, or any other complications that in the opinion of the investigator.
9. Any condition that in the opinion of the investigator would preclude participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide + ADT; Duration of treatment: 28-day cycle of darolutamide treatment and 6 cycles of neoadjuvant therapy.	Drug: Darolutamide+ADT; Drug: Darolutamide Darolutamide 600 mg, (two 300 mg tablets) administered orally twice daily. Swallow tablets whole. Take Darolutamide with food. Drug: ADT GnRH agonist per physicians' choice, orchiectomy is excluded

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathological downstaging	Percentage of patients with tumor downstaging	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs/SAEs	The level of AEs defined by NCI-CTCAE v5.0. Safety assessments will be assessed and documented after initiation of study drug, regardless of relationship to study drug.	Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first
pCR or MRD	Pathologic complete response or Minimal Residual Disease(defined as overall diameter <5 mm)	6 months
PSM	Percentage of patients with positive surgical margins	6 months
Rate of peri-operative complications	including delay in surgery, intra-operative complications, and postoperative complications	within 30 days of surgery
Biochemical complete response	PSA <0.1ng/ml prior to RP	6 months
PSA undetectable rate	PSA<0.02 ng/ml	12 months post-RP
2-year biochemical progression-free survival, bPFS	PSA>0.2 ng/ml	24 months post-RP

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Xijing Hospital of Air Force Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2023
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: March 1, 2023

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
• Other Study ID Numbers: 22440

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