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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06029036
• Other study ID #: 22440
• Status: Recruiting
• Phase: Phase 2
• Start date: August 5, 2023
• Est. completion date: July 31, 2026

Study information

• Verified date: March 2023
• Source: Peking University First Hospital
• Contact: Zhisong He, MD
• Phone: +8610-83572418
• Email: wyj7074[@]sohu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: July 31, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Peking University First Hospital	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Xijing Hospital of Air Force Military Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of pathological downstaging	Percentage of patients with tumor downstaging	6 months
Secondary	pCR or MRD	Pathologic complete response or Minimal Residual Disease(defined as overall diameter <5 mm)	6 months
Secondary	PSM	Percentage of patients with positive surgical margins	6 months
Secondary	Rate of peri-operative complications	including delay in surgery, intra-operative complications, and postoperative complications	within 30 days of surgery
Secondary	Biochemical complete response	PSA <0.1ng/ml prior to RP	6 months
Secondary	PSA undetectable rate	PSA<0.02 ng/ml	12 months post-RP
Secondary	2-year biochemical progression-free survival, bPFS	PSA>0.2 ng/ml	24 months post-RP
Secondary	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