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

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.

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