Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC

Nanjing Medical University

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Prostate Cancer; Intermitent Anti-androgen Therapy

Treatments: Drug: Darolutamide intermittent; Drug: Darolutamide continuous

Study type: Interventional

Funder types: Other

Identifiers

NCT06177015

2023-SR-662

Details and patient eligibility

About

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.

Full description

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

1. When the patient reaches:

2. PSA ≤ 0.2ng/ml

3. Or PSA > 0.2ng/ml but with more that 90% decrease comparing baseline

4. 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.

5. When the patient:

6. PSA > 0.2ng/ml and has not decreased by 90% compared to baseline

7. Or has new metastatic lesions, they will exit the study. Imaging assessment will be conducted every 3 months

Enrollment: 200 estimated patients

Sex: Male

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Continuous treatment group

Active Comparator group

Description:

Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC

Treatment:

Drug: Darolutamide continuous

Intermittent treatment group

Experimental group

Description:

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.

Treatment:

Drug: Darolutamide intermittent