Neoadjuvant Hormone and Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk Prostate Cancer

Neoadjuvant Hormone and Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk Locally Advanced Prostate Cancer and Biomarker Research

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy can fight prostate cancer by androgen deprivation. It is not yet known if neoadjuvant radiation therapy is a more effective therapy for high-risk prostate cancer.

PURPOSE: Two-stage randomized trial to compare the effectiveness and safety of neoadjuvant radiotherapy and hormone therapy followed by radical prostatectomy in men with high-risk locally advanced prostate cancer

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: radiation therapy; Drug: Goserelin 3.6 MG; Procedure: radical prostatectomy

Detailed Description

PRIMARY OBJECTIVE:

I. Success rate of salvage radiation therapy (SRT) measured as pathologic complete response (pCR) or pathologic near complete response (minimal residual disease, MRD) rate.

SECONDARY OBJECTIVES:

I. PSA decline rate after neoadjuvant treatment, rate of undetectable PSA after RP, rate of positive surgical margin, and rate of pathologic down-staging (≤ ypT2N0) II. Biochemical recurrence-free survival rate (from date of randomization). III. Metastasis free survival. IV. Prostate Cancer Death. V. Overall Survival

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive neoadjuvant hormone and radiation therapy, and then radical prostatectomy

ARM II: Participants receive neoadjuvant hormone therapy, and then radical prostatectomy.

After intervention, participants are followed up periodically for up to 20 years.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chi-Shin Tseng, MD; Phone Number: +886223123456; Email: clifford1987tcs@gmail.com

Study Locations

• Taiwan
  • Tapiei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chi-Shin Tseng, MD; Email: clifford1987tcs@gmail.com
    • Principal Investigator: Chao-Yuan Huang, MD, PhD
  • Yunlin County
    • Douliu City/Huwei Township, Yunlin County, Taiwan
      • Recruiting
      • National Taiwan University Hospital Yunlin Branch
      • Contact: Shi-Wei Huang, PhD; Email: Will6438.huang@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men with age from 20 to 75 years old
• Signed an informed consent form (ICF) indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Histologically confirmed adenocarcinoma of the prostate

• High-risk locally advanced disease defined by ≥1 of the following 3 criteria:

  • T3a-3b by DRE or MRI
  • Gleason score ≥ 8 (= Grade group 4)
  • PSA ≥20 ng/ml
• Willing to undergo prostatectomy as primary treatment
• ECOG Performance status 0 or 1

Exclusion Criteria:

• Pathological finding of small cell, ductal or neuroendocrine carcinoma
• Current or prior hormone therapy, radiotherapy, or chemotherapy
• Evidence of metastasis (M1) on images
• Other prior malignancy ≤5 years prior to enrollment
• Any of the following within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary

• Human immunodeficiency virus-positive subjects with 1 or more of the following:

  1. Not receiving highly active antiretroviral therapy
  2. Had a change in antiretroviral therapy within 6 months of the start of screening
  3. Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment)
  4. CD4 count <350 at screening
  5. AIDS-defining opportunistic infection within 6 months of start of screening
• Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
• History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
• Gastrointestinal conditions affecting absorption

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: Neoadjuvant RT and ADT; Intensity modulated radiation therapy (IMRT), with 50 Gy in 25 daily fractions (2 Gy/fraction, 5 fractions weekly) for 5 weeks (week 1 - week 5). Gosereline 3.6mg sc injection at week 1, week 5, and week 9	Radiation: radiation therapy; Intensity modulated radiation therapy (IMRT), with 50 Gy in 25 daily fractions (2 Gy/fraction, 5 fractions weekly) for 5 weeks (week 1 - week 5).; Drug: Goserelin 3.6 MG; Gosereline 3.6mg sc injection at week 1, week 5, and week 9; Other Names: ZOLADEX; Procedure: radical prostatectomy; Eligible patients will undergo robotic-assisted radical prostatectomy and pelvic lymph node dissection
Active Comparator: Neoadjuvant ADT; Gosereline 3.6mg sc injection at week 1, week 5, and week 9	Drug: Goserelin 3.6 MG; Gosereline 3.6mg sc injection at week 1, week 5, and week 9; Other Names: ZOLADEX; Procedure: radical prostatectomy; Eligible patients will undergo robotic-assisted radical prostatectomy and pelvic lymph node dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic outcome	pathologic complete response (pCR) or pathologic near complete response (minimal residual disease, MRD) rate	From date of randomization to the date of radical prostatectomy, up to 100 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA decline percentage	PSA decline is defined as nadir PSA value/baseline PSA value × 100	From date of randomization to 10 years
PSA complete response rate	Complete response is defined as a drop in PSA on protocol treatment to less than 0.2 ng/ml.	From date of randomization to 10 years
PSA Recurrence	Biochemical recurrence is defined as a rise in PSA to 0.2 ng/mL and a confirmatory value of 0.2 ng/mL or greater following radical prostatectomy	From date of randomization to 10 years
Distant Failure	Distant failure rate is estimated by the cumulative incidence method, with failure defined as the first occurrence of distant failure.	From date of randomization to 10 years
Prostate Cancer Death	Prostate cancer death rate us estimated by the cumulative incidence method, with failure defined as death due to prostate cancer or complications of trial.	From date of randomization to 10 years
Overall Survival	Overall survival is estimated by the Kaplan-Meier method, with failure defined as death by any cause.	From date of randomization to 10 years
Progression-free Survival	Progress-free survival is estimated by the Kaplan-Meier method, with failure defined as the first occurrence of PSA failure, local, regional or distant failure, or death from any cause.	From date of randomization to 10 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chao-Yuan Huang, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2041

Study Registration Dates

• First Submitted: May 9, 2021
• First Submitted That Met QC Criteria: May 16, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Goserelin
• Other Study ID Numbers: 202101088RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No