Clinical trial NCT04220398: Neoadjuvant Chemo-hormonal Therapy Combined With Radical Prostatectomy for Locally Advanced Prostate Cancer
Official title: A Prospective, Multicenter, Three-arm, Randomized, Controlled Study Comparing the Efficacy of Neoadjuvant Hormonal Therapy Combined With Systemic Chemotherapy (NCHT), Neoadjuvant Hormonal Therapy (NHT) and Radical Prostatectomy Only in Locally Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer
Chemotherapy Effect
Hormone Sensitive Prostate Cancer
Locally Advanced Prostate Carcinoma
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 475
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 2:2:1
Primary purpose: TREATMENT

Brief summary: To evaluate of the value of radical prostatectomy and extended pelvic lymph node dissection in locally advanced prostate cancer after neoadjuvant hormonal therapy with or without docetaxel chemotherapy.

Detailed description: Using larger sample prospective randomized controlled study design, and comparing neoadjuvant HT combined with docetaxel chemotherapy to neoadjuvant HT followed by RP and extended lymph node dissection to determine whether neoadjuvant HT combined with docetaxel chemotherapy can more effectively improve biochemical progression-free survival of locally advanced prostate cancer patients.

Further analysis was performed to determine whether the treatment regimen helped to prolong the radiologic progression-free survival (rPFS) or OS in these patients.

The pathological changes of tumor before and after neoadjuvant treatment were also analyzed. To search for the important risk factors influencing the long-term prognosis of these patients, the safety characteristics of patients in different treatment groups were analyzed. Therefore, it can provide the basis for the formulation of the optimal treatment plan for locally advanced prostate cancer, prolong the survival time of patients and improve the quality of life.

Study design: Prospective，Multicenter, Open-label, Parallel group, Randomized (2:2:1) Controlled , Clinical Trial

Study group: Newly diagnosed, untreated cT3a-cT4 or any cT, cN1 in locally advanced hormone-sensitive prostate cancer.

Study group number: 475 cases, Randomized 2:2:1

Eligibility criteria: Inclusion Criteria:

1. 18≤ Aged \<75 years, male;
2. Histology or cytology diagnosis: Prostate adenocarcinoma;
3. ECOG performance Status ≤1; Expected lifetime ≥10 years;
4. Without clinical or radiographic metastases in 6 months (Bone scan, MRI or pelvic enhanced CT scan, PET-CT) before randomized;
5. The patients of locally advanced prostate cancer need to satisfy at least one of the following requirements: clinical stageT3a-T4, N0, M0; any T, N1, M0;
6. Without Androgen Blockade Treatment in 4 weeks before randomized;
7. Without radiographic treatment towards primary tumour;
8. Without opioids (including codeine and dextropropoxyphene) relieving relevant pain of cancer;
9. Without azole drugs (such as fluconazole, itraconazole);
10. Important laboratory indicators are as follows:

    1. Haemoglobin ≥90g/L
    2. ANC ≥ 1500/μL
    3. PLT≥100\*10\^9/L
    4. K+≥3.5mmol/L
    5. AST or ALT ≤1.5 times upper limit of normal (ULN), TBIL should be ≤ULN (except patients with certified Gilbert syndrome) and ALP≤5ULN
    6. ALB≥30g / L
    7. calculated Ccr\>60 ml/min, serum creatinine ≤ ULN
11. Without swallowing disease, able to swallow the whole piece of drugs;
12. Without other tumour chemotherapy history, without chemotherapy and endocrine therapy contraindications;
13. If patient's spouse is at her childbearing age, the patient needs to agree that effective contraception should be taken during the treatment and 4 months after the operation.
14. Subjects volunteer to participate, the subject must sign an informed consent form (ICF), indicating the understanding of the purpose and the required procedures of the study, and willing to participate in the study. Subjects must be willing to comply with the prohibitions and restrictions set forth in the program.

Exclusion Criteria:

1. The pathology result of prostate is neuroendocrine prostate cancer, including small cell carcinoma;
2. Previous cytotoxic chemotherapy or biological therapy for prostate cancer;
3. Contraindications to prednisone, such as active infections or other disorders;
4. Patients with chronic disease needed to be given dose of prednisone (each time 5mg, bid a day) exceed the dose in the study;
5. High blood pressure with poor control of drugs (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥95mmHg);
6. Active or symptomatic viral hepatitis or other chronic liver disease, known infected with human immunodeficiency virus (HIV);
7. A disease history of pituitary or adrenal dysfunction;
8. Patients with active autoimmune disease who need hormone therapy;
9. Heart disease with clinical significance, including: myocardial infarction or arterial thrombosis occurred in the past 6 months; severe or unstable angina; New York Heart Association grade III or IV heart disease (Appendix 4); atrial fibrillation or other arrhythmias that require treatment;
10. Subjects who participated in other clinical studies within a month before the first use of chemotherapy; (the elution time is at least 5 times the half-life time of the study drug if the half-life time is too long.)
11. Patients with a history of hypersensitivity to Taxanes or docetaxel
12. Patients who are concomitantly receiving strong CYP3A4 inhibitors
13. Other circumstances considered inappropriate by investigator.

Primary outcomes:
measure: bPFS (Biochemical progression-free survival)
timeFrame: about 2 years
Secondary outcomes:
measure: The 1-year biochemical progression-free survival (bPFS) rate
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 5-10 years
measure: Radiographic progression-free survival (rPFS)
timeFrame: 3-5 years
measure: TTPP
timeFrame: 1-3 years
measure: ECOG score progression-free survival
timeFrame: 3-5 years
Other outcomes:
Locations:
Study officials:
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