Androgen Deprivation Therapy Combined With Docetaxel for High Risk Prostate Cancer

A Randomized, Controlled, Single Center Clinical Trial to Evaluate the Efficacy and Safety of Neoadjuvant Therapy With Androgen Deprivation Therapy Combined With Docetaxel for High Risk and Very High Risk Prostate Cancer

This randomized, controlled, single center clinical trial aims to evaluate the efficacy and safety of Androgen Deprivation Therapy Combined with Docetaxel for High Risk Prostate Cancer with a six-month treatment cycle.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoadjuvant Therapy \ High Risk Prostate Cancer \ Docetaxel
• Intervention / Treatment: Drug: Docetaxel injection; Drug: Triptorelin Pamoate for Injectable Suspension; Drug: Prednisone Acetate Tablets

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients must be ≥ 18 and ≤75 years of age.
• All patients must have a histologically or cytologically diagnosis of prostate cancer and must be eligible for radical prostatectomy.

• All patients must undergo thorough tumor staging and meet one of the following criteria:

  1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T3,
  2. Gleason score of primary tumor ≥ 8, 3.prostate specific antigen (PSA) ≥20 ng/ml.
  3. Eastern Cooperative Oncology Group (ECOG) physical condition score ≤ 1.
  4. Patients must have adequate hematologic function, within 28 days prior to registration as evidenced by: white blood cell (WBC) ≥ 4.0 × 109 /L, platelets≥ 100 × 109 / L, hemoglobin ≥ 9 g / dL, and international normalized ratio (INR) < 1.5.
  5. Patients must have adequate hepatic function, within 28 days prior to registration, as evidenced by: total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN),and SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN.
  6. Patients must have adequate renal function, within 28 days prior toregistration, as evidenced by serum creatinine ≤2×ULN
• 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.

Exclusion Criteria:

• Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible.
• Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor < T3, Gleason score of primary tumor < 8, and prostate specific antigen (PSA) <20 ng/ml.
• Patients with clinical or radiological evidence of extra-regional lymph node metastases or bone metastases or visceral metastases are not eligible.
• Patients who have previously received androgen deprivation therapy (medical or surgical) or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy are not eligible.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Androgen Deprivation Therapy with Docetaxel; All subjects in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus docetaxel and prednisone, as per standard of care. Triptorelin pamoate (Diphereline) 15mg will be used once per 12 weeks. Docetaxel (75 mg/m2 body surface area) will be administered as intravenous drip every 3 weeks for 6 cycles. Robot assisted radical prostatectomy will be followed in 2 weeks when 24-week treatment cycle is finished.	Drug: Docetaxel injection; 75 mg/m2 body surface area every 3 weeks for 6 cycles before robot assisted radical prostatectomy; Drug: Triptorelin Pamoate for Injectable Suspension; 15mg every 12 weeks; Drug: Prednisone Acetate Tablets; 5 mg oral low dose prednisone, once daily
Active Comparator: ADT alone; All subjects in this arm will receive LHRHa alone for 24 weeks before receiving robot assisted radical prostatectomy. Triptorelin Pamoate 15mg will be administered once per 12 weeks.	Drug: Triptorelin Pamoate for Injectable Suspension; 15mg every 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate	The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.	up to 8 months
pCR or MRD rate	The proportion of patients with pCR or MRD. Pathologic complete response (pCR): defined as no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy. Minimal Residual Disease (MRD): defined as residual tumors with maximum diameter of 3 mm or less after radical prostatectomy.	up to 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging Response Rate	The proportion of subjects whose primary tumor is in complete remission on imaging or residual tumor's maximum diameter is less than 0.5cm.	up to 8 months
Rate of Stage Degradation	Clinical or pathological stage degradation after neoadjuvant therapy	up to 8 months
Rate of Positive Surgical Margins	The proportion of subjects with positive surgical margins after radical prostatectomy.	up to 8 months
Rate of Complete Serum Remission	The proportion of subjects whose PSA is less than or equal to 0.2 ng/ml after 6 months of treatment.	up to 8 months
Operative time (min)	The operative time(min) of radical prostatectomy.	12 month
Estimated blood loss (ml)	Estimated blood loss (ml) during the process of radical prostatectomy.	12 month
Hospital length of stay (day)	The hospitalization time, recorded in day.	12 month
Drainage duration (day)	Length of drainage duration, recorded in day.	12 month
Incidence of complications (%)	The proportion of subjects who suffer from major complications.	12 month
Recovery time of urinary continence (day)	The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day.	12 month
biochemical progression-free survival (bPFS)	Biochemical progression was defined as two consecutive rising PSA values that were above 0.2ng/ml at least one month apart, or starting adjuvant therapy after surgery including radiotherapy, ADT or anti-androgen therapy. The time for bPFS was measured from randomization to biochemical progression or death from any cause.	3 years
metastasis-free survival (MFS)	Time from date of randomization to date of evidence of systemic disease on bone scan or cross-sectional imaging.	5 years
Serum complete response rate	Serum complete response rate, defined as the proportion of participants with PSA ≤ 0.1 ng/mL after 6-month neoadjuvant therapy.	after 6 month neoadjuvant therapy and before surgery
Rate of extracapsular extension	The proportion of patients with extracapsular extension on pathologic specimens after neoadjuvant therapy.	12 month
Rate of positive lymph node	The proportion of patients with positive lymph node on pathologic specimens after neoadjuvant therapy.	12 month

Collaborators and Investigators

• Sponsor: Hongqian Guo

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): December 1, 2020
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Estimate): December 29, 2022
• Last Update Submitted That Met QC Criteria: December 24, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Docetaxel; Prednisone; Triptorelin Pamoate
• Other Study ID Numbers: IUNU-PC-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No