Clinical trial NCT06177015: Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC
Official title: Randomized Controlled Study on the Efficacy and Safety of Intermittent Darolutamide Treatment in the Triple Therapy of Metastatic Hormone Sensitive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Prostate Cancer
Intermitent Anti-androgen Therapy
Keywords: triple treatment regimen
mHPSC
Darolutemide
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-12-20
Enrollment: 200
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two independent arms
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Radiographic Progression Free Survival
timeFrame: 36 months
measure: Overall Survival
timeFrame: 36 months
Secondary outcomes:
measure: Time to castration-resistant prostate cancer
timeFrame: 36 months
measure: Time to pain progression
timeFrame: through study completion, an average of 3 year
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Urology dpt, First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Urology Dpt, First Affiliated Hospital of Nanjing Medical University
name: Lixxin Hua
role: PRINCIPAL_INVESTIGATOR
References: