Neoadjuvant Chemo-hormonal Therapy Combined With Radical Prostatectomy for Locally Advanced Prostate Cancer

Not Applicable

Not yet recruiting

• Conditions: Prostate Cancer; Hormone Sensitive Prostate Cancer; Chemotherapy Effect; Locally Advanced Prostate Carcinoma
• Interventions: Drug: Neoadjuvant hormone therapy; Drug: Neoadjuvant chemotherapy combined with hormone therapy; Procedure: Radical Prostatectomy (RP)+ extended lymph node dissection

• Registration Number: NCT04220398
• Lead Sponsor: RenJi Hospital

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

Study Timeline

• Status Verified: 2020-01
• Study First Submitted: 2020-01-02
• Study First Submitted QC: 2020-01-04
• Last Update Submitted: 2020-01-04
• Study First Posted: 2020-01-07
• Last Update Posted: 2020-01-07
• Study Start: 2020-01-10
• Primary Completion: 2022-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 475

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NCHT Group	Radical Prostatectomy (RP)+ extended lymph node dissection	Neoadjuvant chemotherapy combined with hormone therapy, Radical Prostatectomy (RP)+ extended lymph node dissection
NHT Group	Neoadjuvant hormone therapy	Neoadjuvant hormonal therapy, radical Prostatectomy (RP)+ extended lymph node dissection.
NHT Group	Radical Prostatectomy (RP)+ extended lymph node dissection	Neoadjuvant hormonal therapy, radical Prostatectomy (RP)+ extended lymph node dissection.
NCHT Group	Neoadjuvant chemotherapy combined with hormone therapy	Neoadjuvant chemotherapy combined with hormone therapy, Radical Prostatectomy (RP)+ extended lymph node dissection
RP Group	Radical Prostatectomy (RP)+ extended lymph node dissection	Radical Prostatectomy (RP)+ extended lymph node dissection alone.

Primary Outcome Measures

Name	Time	Method
bPFS (Biochemical progression-free survival)	about 2 years	Biochemical recurrence-free survival (bPFS): defined as the time from randomization to biochemical recurrence. The definition of biochemical recurrence is as follows: in the case of normal testosterone levels, the PSA was \>0.2 ng/ml twice for more than 4 consecutive weeks.

Secondary Outcome Measures

Name	Time	Method
The 1-year biochemical progression-free survival (bPFS) rate	1 year	The ratio of patients whose consecutive postoperative PSA \<0.2ng/ml within 1-year.
Overall survival (OS)	5-10 years	The time from randomization to death due to all causes.
Radiographic progression-free survival (rPFS)	3-5 years	The time from randomization to first confirmed imaging progression or death (whichever first is counted). Imaging progression was defined as one of the following: a. Progression of soft tissue lesions as defined in the revised RECIST 1.1 (Appendix 8) found by CT or MRI. b. Confirmation of bone metastasis lesions by ECT or PET-CT examination.
TTPP	1-3 years	The time from randomization to the time when PSA increased by 25%.
ECOG score progression-free survival	3-5 years	The time from treatment to the time of ECOG score progression.