Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC

Randomized Controlled Study on the Efficacy and Safety of Intermittent Darolutamide Treatment in the Triple Therapy of Metastatic Hormone Sensitive Prostate Cancer

To evaluate the efficacy and safety of intermittent use of darolutamide compared to long-term use in combination with ADT and docetaxel in the treatment of mHSPC patients.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Prostate Cancer; Intermitent Anti-androgen Therapy
• Intervention / Treatment: Drug: Darolutamide continuous; Drug: Darolutamide intermittent

Detailed Description

Patients will firstly receive 6 months of darolutamide in combination with docetaxel and ADT treatment.

1. When the patient reaches:

1. PSA ≤ 0.2ng/ml
2. Or PSA > 0.2ng/ml but with more that 90% decrease comparing baseline
3. Without newly discovered metastatic lesions. They will be randomly assigned in a 1:1 ratio to either continuous treatment group or intermittent treatment group (1) Continuous treatment group: Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC; (2) Intermittent treatment group: Only ADT as background treatment without Darolutamide. PSA check every three months, when the patient's PSA > 1ng/ml (or PSA > 1ng/ml and PSA has risen by more than 20% comparing baseline), restart the darolutamide, until mCRPC.

2. When the patient:

1. PSA > 0.2ng/ml and has not decreased by 90% compared to baseline
2. Or has new metastatic lesions, they will exit the study. Imaging assessment will be conducted every 3 months

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shangqian Wang; Phone Number: +862568303186; Email: wsq5501@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Urology dpt, First Affiliated Hospital of Nanjing Medical University
      • Contact: Shangqian Wang, M.D.,PhD.; Phone Number: 68303186; Email: wsq5501@126.com
      • Principal Investigator: Lixin Hua, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for this study:

1. Male aged ≥18 years;
2. Histologically or cytologically confirmed prostate adenocarcinoma;
3. Metastatic disease (confirmed by conventional imaging);
4. ECOG performance status of 0-1;
5. Suitable for ADT and docetaxel treatment;
6. Good bone marrow, kidney, and liver function:

1. (1) Hematological examination (no blood transfusion or use of hematopoietic growth factors within 7 days before screening):

1. Hemoglobin (HB) ≥ 90g/L; 2. Absolute neutrophil count (ANC) ≥ 1.5×109/L; 3. Platelets (PLT) ≥ 80×109/L; 2. (2) Blood biochemistry examination (no blood transfusion or albumin within 7 days before screening):

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
2. Total bilirubin (TBIL) ≤ 2.0 × ULN;
3. Serum creatinine (Cr) ≤ 2.0×ULN;

7. Willing to participate in this study, sign an informed consent form, and have good compliance

Exclusion Criteria:

1. No metastatic disease;
2. Prior treatment with: a) Second-generation ARis or other experimental ARis b) CYP17 enzyme inhibitors such as abiraterone acetate or oral ketoconazole for anti-tumor treatment of prostate cancer c) Chemotherapy or immunotherapy prior to randomization for prostate cancer
3. Received radiotherapy within 2 weeks before starting 6 months of darolutamide + docetaxel + ADT treatment;
4. Stroke, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass surgery, congestive heart failure (New York Heart Association class III or IV);
5. History of malignant tumors;
6. Planned receipt of other anti-tumor treatment during the study treatment period;
7. Known allergy to the above drug components;
8. Difficulty swallowing, chronic diarrhea, intestinal obstruction, and various factors affecting drug intake and absorption;
9. Refusal to sign the informed consent form;
10. Investigator's opinion that the participant is not suitable for inclusion.

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
Active Comparator: Continuous treatment group; Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC	Drug: Darolutamide continuous; standard of care; Other Names: Darolutamide
Experimental: Intermittent treatment group; Only ADT as background treatment without Darolutamide. PSA check every three months, when the patient's PSA > 1ng/ml (or PSA > 1ng/ml and PSA has risen by more than 20% comparing baseline), restart the darolutamide, until mCRPC.	Drug: Darolutamide intermittent; experimental group; Other Names: Darolutamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression Free Survival	rPFS	36 months
Overall Survival	OS	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to castration-resistant prostate cancer	Time to mCRPC	36 months
Time to pain progression	TTPP	through study completion, an average of 3 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Lixxin Hua, Urology dpt, First Affiliated Hospital of Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: mHPSC; triple treatment regimen; Darolutemide
• 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: 2023-SR-662

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