Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC

Phase 3

Recruiting

• Conditions: Metastatic Prostate Cancer; Intermitent Anti-androgen Therapy
• Interventions: Drug: Darolutamide continuous; Drug: Darolutamide intermittent

• Registration Number: NCT06177015
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

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.

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 Timeline

• Status Verified: 2023-12
• Study Start: 2023-12-11
• Study First Submitted: 2023-12-11
• Study First Submitted QC: 2023-12-11
• Study First Posted: 2023-12-20
• Last Update Submitted: 2023-12-22
• Last Update Posted: 2023-12-26
• Primary Completion: 2025-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 200

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:

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

8. 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):

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN

10. Total bilirubin (TBIL) ≤ 2.0 × ULN;

11. Serum creatinine (Cr) ≤ 2.0×ULN;

12. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Continuous treatment group	Darolutamide continuous	Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC
Intermittent treatment group	Darolutamide intermittent	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.

Primary Outcome Measures

Name	Time	Method
Radiographic Progression Free Survival	36 months	rPFS
Overall Survival	36 months	OS

Secondary Outcome Measures

Name	Time	Method
Time to castration-resistant prostate cancer	36 months	Time to mCRPC
Time to pain progression	through study completion, an average of 3 year	TTPP

Trial Locations

Locations (1)

Urology dpt, First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China