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

NCT ID: NCT04220398

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 475 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-10
• Study Completion Date: 2024-12-31

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

Conditions

Prostate Cancer; Chemotherapy Effect; Hormone Sensitive Prostate Cancer; Locally Advanced Prostate Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NCHT Group

Neoadjuvant chemotherapy combined with hormone therapy, Radical Prostatectomy (RP)+ extended lymph node dissection

Group Type: EXPERIMENTAL

Neoadjuvant chemotherapy combined with hormone therapy

Intervention Type: DRUG

Docetaxel 75mg/m2 IV (every 3 weeks) +Prednisone 5mg BID orally + HT (Bicalutamide Tablets, 50mg QD orally; Goserelin, 3.6mg, subcutaneous injection, q28d), 4-6 cycles

Radical Prostatectomy (RP)+ extended lymph node dissection

Intervention Type: PROCEDURE

Radical Prostatectomy (RP)+ extended lymph node dissection: Within three months after neoadjuvant treatment.

Treatment after prostatectomy: There will not have any drug treatment after surgery until disease progression.

Pelvic lymph node dissection is required to reach the level of bilateral iliac artery. If the postoperative pathology indicated positive incisional margin or pelvic lymph node metastasis, pelvic adjuvant radiotherapy should be performed within 3 months after surgery.

NHT Group

Neoadjuvant hormonal therapy, radical Prostatectomy (RP)+ extended lymph node dissection.

Group Type: ACTIVE_COMPARATOR

Neoadjuvant hormone therapy

Intervention Type: DRUG

HT (Bicalutamide Tablets, 50mg QD orally; Goserelin, 3.6mg, subcutaneous injection, q28d), 3-6 cycles

Radical Prostatectomy (RP)+ extended lymph node dissection

Intervention Type: PROCEDURE

Radical Prostatectomy (RP)+ extended lymph node dissection: Within three months after neoadjuvant treatment.

Treatment after prostatectomy: There will not have any drug treatment after surgery until disease progression.

Pelvic lymph node dissection is required to reach the level of bilateral iliac artery. If the postoperative pathology indicated positive incisional margin or pelvic lymph node metastasis, pelvic adjuvant radiotherapy should be performed within 3 months after surgery.

RP Group

Radical Prostatectomy (RP)+ extended lymph node dissection alone.

Group Type: OTHER

Radical Prostatectomy (RP)+ extended lymph node dissection

Intervention Type: PROCEDURE

Radical Prostatectomy (RP)+ extended lymph node dissection: Within three months after neoadjuvant treatment.

Treatment after prostatectomy: There will not have any drug treatment after surgery until disease progression.

Pelvic lymph node dissection is required to reach the level of bilateral iliac artery. If the postoperative pathology indicated positive incisional margin or pelvic lymph node metastasis, pelvic adjuvant radiotherapy should be performed within 3 months after surgery.

Interventions

Neoadjuvant chemotherapy combined with hormone therapy

Docetaxel 75mg/m2 IV (every 3 weeks) +Prednisone 5mg BID orally + HT (Bicalutamide Tablets, 50mg QD orally; Goserelin, 3.6mg, subcutaneous injection, q28d), 4-6 cycles

Intervention Type: DRUG

Neoadjuvant hormone therapy

HT (Bicalutamide Tablets, 50mg QD orally; Goserelin, 3.6mg, subcutaneous injection, q28d), 3-6 cycles

Intervention Type: DRUG

Radical Prostatectomy (RP)+ extended lymph node dissection

Radical Prostatectomy (RP)+ extended lymph node dissection: Within three months after neoadjuvant treatment.

Treatment after prostatectomy: There will not have any drug treatment after surgery until disease progression.

Pelvic lymph node dissection is required to reach the level of bilateral iliac artery. If the postoperative pathology indicated positive incisional margin or pelvic lymph node metastasis, pelvic adjuvant radiotherapy should be performed within 3 months after surgery.

Intervention Type: PROCEDURE

Other Intervention Names

NCHT; NHT; RP+ePLND

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Wei Xue

Role: CONTACT

xuewei@renji.com

08613801931604

Chenfei Chi

Role: CONTACT

chichenfei@renji.com

08613661633570

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PCANT-20

Identifier Type: -

Identifier Source: org_study_id