Feasibility Study of Inductive Apalutamide Therapy with Radical Prostatectomy in Locally Advanced T4 High-Risk Prostate Cancer Patients

Trial ID: 2023-509837-37-00
Sponsor: University Of Saarland

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Diseases & Conditions

Prostate cancer

Objectives

The primary objective of this study is to evaluate the **operability** in patients with locally advanced T4 high-risk **prostate cancer** following inductive preprostatectomy treatment with **apalutamide** combined with androgen deprivation therapy (ADT) for up to 6 months. This assessment is clinically relevant as it aims to determine the potential for surgical intervention in a high-risk patient population, which could significantly impact treatment outcomes and survival rates.

Secondary objectives include:

Assessing the feasibility of the treatment regimen.
Evaluating the effect of the treatment on patients' quality of life.
Characterizing prostate-specific antigen (PSA) levels post-surgery without further therapy and achieving biochemical complete remission 6 months after surgery.
Describing the time to biochemical recurrence (BCR).
Assessing complete pathological response and negative margin status.
Evaluating the safety and tolerability of the treatment.

Participants

The clinical trial involves **male** participants aged 18 to 80 years, diagnosed with locally advanced T4 high-risk **prostate cancer**. The study population is exclusively male, with no female subjects included, and does not involve any vulnerable populations. Participants are required to have a histologically confirmed adenocarcinoma of the prostate without complete neuroendocrine differentiation or small cell features. They must be considered primarily inoperable due to a fixed mass, as determined by digital rectal examination and confirmed by advanced disease in MRI. The trial population was selected based on specific inclusion criteria, including an Eastern Cooperative Oncology Group Performance Status of 0 or 1, indicating that patients are fit and willing to undergo radical prostatectomy within 6 to 9 months after the start of study treatment. Participants must have adequate organ function, as determined by specific laboratory values, and must not have undergone irradiation of the pelvis. They should be able to swallow whole study drug tablets and are not candidates for radiotherapy or have denied radiotherapy. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed to evaluate the **operability** of patients with locally advanced T4 high-risk **prostate cancer** following inductive pre-prostatectomy treatment with **apalutamide** plus androgen deprivation therapy (ADT). This study is a Phase II, randomized, double-blind, controlled trial with an estimated duration from February 25, 2022, to March 31, 2025. The trial involves the administration of apalutamide in the form of film-coated tablets, with a maximum daily dose of 240 mg, for a treatment period of up to six months. The primary endpoint is the proportion of patients deemed operable, assessed through MRI, transrectal ultrasound, and clinical examination by experienced uro-oncological surgeons.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of adenocarcinoma, and adequate organ function. Follow-up visits will occur throughout the treatment period to monitor the patient's response and any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints, including pathological response and biochemical remission. The expected length of participant involvement is approximately six to nine months, with conditions for early termination including significant adverse events or failure to achieve the desired PSA nadir.

Secondary endpoints include the proportion of patients with complete pathological response, negative surgical margins, and post-prostatectomy biochemical remission. Additional assessments will measure changes in quality of life scores and the incidence of post-surgical complications. The trial will also monitor safety and tolerability, focusing on adverse events and laboratory abnormalities. Participants are required to adhere to specific guidelines, such as using contraception and refraining from sperm donation during and after the study. The trial aims to provide valuable insights into the efficacy of apalutamide in improving surgical outcomes for patients with high-risk prostate cancer.

Treatment

The clinical trial involves the administration of the experimental medication **Apalutamide**, marketed under the product code JNJ-56021927. This medication is provided in the form of a **film-coated tablet** and is intended for **oral use**. The maximum daily dose of Apalutamide is 240 mg, with a total maximum dose of 240 mg per day. The treatment period is set for a maximum of 4 months. Apalutamide is a non-steroidal antiandrogen, chemically synthesized, and is not formulated for pediatric use. The medication is manufactured by Janssen-Cilag International N.V.

In addition to the experimental treatment, the study protocol includes the use of standard-of-care therapy, specifically androgen deprivation therapy (ADT), which is administered in combination with Apalutamide. The primary objective of this combination therapy is to assess operability in patients with locally advanced T4 high-risk prostate cancer. The dosing schedule and administration of ADT will follow standard clinical guidelines, and participant compliance will be monitored throughout the study to ensure adherence to the treatment regimen.

Efficacy

The efficacy of the clinical trial investigating the use of **apalutamide** in combination with androgen deprivation therapy (ADT) for patients with locally advanced T4 high-risk prostate cancer will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of patients achieving operability, as determined by magnetic resonance imaging (MRI), transrectal ultrasound, and clinical examination conducted by two experienced uro-oncological surgeons, following up to six months of inductive pre-prostatectomy treatment.

Secondary endpoints include the proportion of patients with a complete pathological response (pT0) in prostatectomy specimens, the proportion of patients with negative surgical margins according to histology results, and the proportion of patients achieving complete biochemical remission, defined as non-detectable serum prostate-specific antigen (PSA) six months post-surgery without hormonal treatment. Additional secondary endpoints involve the assessment of post-prostatectomy complications requiring surgical re-intervention, the achievement of PSA nadir during inductive treatment, and changes in patient-reported outcomes such as the FACT-P and EQ-5D-3L scores at various study visits. The trial will also evaluate the time to biochemical recurrence (BCR) and changes in hematologic parameters and serum testosterone levels from baseline.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male of 18 to 80 years of age, inclusive
Histologically confirmed adenocarcinoma of the prostate without complete neuroendocrine differentiation or small cell features
cT4 PCa, considered as primary inoperable because of a fixed mass defined by digital rectal examination, confirmed by advanced disease in MRI
Eastern Cooperative Oncology Group Performance Status 0 or 1, patients must and are expected to be fit and willing to undergo radical prostatectomy within 6 to 9 months after start of study treatment
Adequate organ function determined by the following laboratory values: a.Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin less than twice the upper limit of normal b.Platelets ≥100,000/L, independent of transfusion and/or growth factors within 1 month prior to enrolment
At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors and estrogens prior to enrolment
No irradiation of the pelvis
Be able to swallow whole study drug tablets
Not candidate for radiotherapy or who deny radiotherapy
Must agree to wear a condom when engaging in any activity that allows for passage of ejaculate to another person while on study drug and for 3 months following the last dose of study drug
Must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last dose of IMP
Must sign an ICF indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study.

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Exclusion Criteria

Presence of distant metastasis (clinical stage M1) after MRI, CT abdomen and bone scan Note: Patients with distant metastases only detectable in PSMA-PET/CTs are allowed to be included in the trial when conventional imaging (CT and bone scan) is negative for distant metastases
Pathological finding consistent with small cell, ductal, or complete neuroendocrine prostate cancer
Prior treatment with second generation anti-androgens
Prior treatment with CYP17 inhibitors
Prior treatment with systemic glucocorticoids ≤4 weeks prior to enrolment or patient expected to require long-term use of corticosteroids during the study
Use of 5-α reductase inhibitors (eg, dutasteride, finasteride) ≤4 weeks prior to enrolment
Major surgery ≤4 weeks prior to enrolment
Prior treatment with radiopharmaceutical agents
Prior chemotherapy for prostate cancer
History of any pelvic radiation
Bilateral orchiectomy
History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to enrolment; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months; uncontrolled hypertension; history of seizure or convulsion; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures
Presence of any of the following cardiologic criteria: a) Mean resting QTc >470 msec b) In patients with a history of risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval, the benefit-risk ratio including the potential for Torsade de pointes will be carefully assessed and patients will be excluded if the benefit-risk ratio is considered as unfavorable.
Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
Any active infection requiring systemic therapy
Known or suspected contraindications or hypersensitivity to apalutamide, or GnRH agonists or any of the components of the formulations
Patient is eligible for PROTEUS study (all patients with operable, non T4 disease)
Patient has received another investigational medication (including investigational vaccines) or used another invasive investigational medical device within 30 days before the planned first dose of the IMP of this study or is currently enrolled in another investigational study.