Clinical trial NCT05461261: The Efficacy and Safety of Docetaxel Combined With Platinum for Metastatic Hormone-sensitive Prostate Cancer
Official title: A Randomized Controlled Trial to Evaluate the Efficacy and Safety of Docetaxel Combined With Platinum-based Drugs Compared With Docetaxel Alone for Metastatic Hormone-sensitive Prostate Cancer Patients Carrying DNA Repair Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hormone Sensitive Metastatic Prostate Cancer
DNA Damage Repair Deficiency
Chemotherapy Effect
Chemotherapeutic Toxicity
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2022-07-18
Enrollment: 50
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized controlled trial was designed to evaluate the efficacy and safety of Docetaxel combined with Platinum-based drugs compared with Docetaxel alone for metastatic hormone-sensitive prostate cancer patients carrying DNA repair mutation.


Eligibility criteria: Inclusion Criteria:

* Patients must be ≥ 40 and ≤75 years of age.
* All patients must have been histologically diagnozed of prostate cancer.
* Metastatic disease confirmed by imaging: positive bone scan, or soft tissue or visceral metastases confirmed by abdominal/pelvic/chest contrast CT or MRI or PSMA PET-CT scan.
* Participants who were treated with androgen deprivation therapy (ADT) (LHRH agonist/antagonist or orchectomy) with or without first-generation anti-androgens within 12 weeks prior to random assignment must maintain serum testosterone castration levels, i.e., ≤50 ng/dL (≤ 1.75 nmol/L) during the study period. First-generation anti-androgens must be discontinued at least 1 day before the start of study therapy.
* Participants must carry one of the following DNA repair gene mutation: 1) HRR-related genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L; 2) Lynch syndrome-related genes: EPCAM, MLH1, MSH2, MSH6, PMS2.
* Eastern Cooperative Oncology Group (ECOG) physical condition score ≤1.
* Patients must have adequate hematologic function, hepatic function and renal function within 28 days prior to registration.
* Patients must participate voluntarily and sign an informed consent form(ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol.
* Sexually active male subjects and their partner must agree the use of condoms as an effective contraceptive method and to avoid sperm donation during the whole treatment and within 4 weeks after the end of treatment.

Exclusion Criteria:

* Patients with neuroendocrine, small cell, or signet ring cell histological features are not eligible.
* Patients with brain/meningeal metastases are not eligible..
* Patients previously received any of the following treatments are not eligible: 1) LHRH agonists/antagonists within 12 weeks prior to the start of study therapy; 2) Second generation androgen receptor (AR) inhibitors, such as enzaluamine, dalotamide, apatamide, etc; 3) Cytochrome P17 enzyme inhibitors (e.g., abiraterone acetate or oral ketoconazole) as antitumor therapy for PCa; 4) Chemotherapy (including docetaxel) or immunotherapy for PCa; 5) Systemic corticosteroids \> 10 mg/day equivalent dose of prednisone within 28 days prior to random assignment.
* Patients who were known to have hypersensitivity to any research drug or similar drug are not eligible.
* Patients received local treatments such as pre-focal treatment,radiotherapy and palliative endoscopic resection
* Patients with severe or uncontrolled concurrent infections are not eligible.
* Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration.
* Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
* Patients must not have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled.
* Patients with mental illness, mental disability or inability to give informed consent are not eligible.

Primary outcomes:
measure: Time to Metastatic Castration-Resistant Prostate Cancer (mCRPC)
timeFrame: up to 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: up to 5 years
measure: rPFS
timeFrame: up to 5 years
measure: Time to PSA progression
timeFrame: up to 5 years
measure: Time to subsequent anti-tumor therapy
timeFrame: up to 5 years
measure: Adverse events
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
state: Jiangsu
Study officials:
affiliation: Nanjing Drum Tower Hospital, affiliated to medical school of Nanjing University Locations: China, Jiangsu
name: Hongqian Guo
role: STUDY_CHAIR
References: