Adjuvant Apalutamide in Subjects With High-risk Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy

NCT04295447 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: UKM17_0018
• Study Type: interventional
• Target: 190
• Locations: 2 countries
• Sites: 21

Brief Summary

The primary objective of this trial is to determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE) in comparison to standard of care (SOC).

Conditions

Prostatic Neoplasms

Keywords

prostate cancer; apalutamide; radical prostatectomy; randomized; high risk adenocarcinoma; neoplasm

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS).

  This endpoint is defined as time interval from randomization until BCR (irrespective of the PSADT), metastases, or death from any cause, whichever occurs first. BCR is defined as a PSA ≥ 0.2 ng/ml that has risen on at least two separate occasions at least four weeks ± 3 days apart and measured by the central PSA-lab. The time of BCR is then backdated to the time of the first increased PSA measurement. Metastatic disease will be defined as the presence of bone metastases visualized on bone scan prostate cancer working group 3 (PCWG3)-criteria; and/or visceral (e.g. liver, lung, brain) or extra-pelvic nodal metastases visualized on CT scan (or MRI scan) (RECIST 1.1-criteria). Evaluations will be performed every 6 months once BCR occurred or sooner if clinically indicated. For a patient with none of these events before the end of follow-up, observation of PFS will be censored at the date of his date of last contact.

  From date of randomization until the date of first documented progression (BCR or metastases) or date of death from any cause, whichever came first, assessed up to 7 years"

Secondary Outcomes (2)

• PSA doubling time (PSADT)

  If BCR occurs up to 6 months later

• Incidence of Adverse Events [Safety and Tolerability]

  From date the informed consent is signed until BCR occured and PSADT was calculated or when distant metastasis occurred (both with or without BCR) or date of death from any cause, whichever came first, assessed up to 7 years.

Study Arms (2)

Standard of care

OTHER

1. Observation only or 2. An optional adjuvant radiation of the prostate bed in case of positive surgical margin

Other: Standard of care

Apalutamide

EXPERIMENTAL

30 cycles apalutamide 240 mg (4 x 60 mg) once daily on days 1-28 of a 28-day cycle in addition to standard of care

Other: Standard of care; Drug: Apalutamide 60Mg Tab

Interventions

Standard of care OTHER

1. Observation only or 2. An optional adjuvant radiation of the prostate bed in case of positive surgical margin

Apalutamide; Standard of care

Apalutamide 60Mg Tab DRUG

(4 x 60 mg) once daily on days 1-28 of a 28-day cycle

Apalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF).
• Men ≥ 18 years of age.
• Patients with histologically confirmed adenocarcinoma of the prostate after radical prostatectomy.
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.
• Patients after radical prostatectomy must meet the d'Amico criteria for high risk of disease recurrence: i.e. one of the following after RPE: 1) Gleason score ≥8, any T-stage, any initial PSA (iPSA) or 2) Gleason score 6 or 7, any iPSA and ≥pT3c or 3) iPSA \>20 ng/ml, any Gleason score, any T-stage.
• Patients have to have recovered from radical prostatectomy within four weeks to be able to take part in the study.
• PSA-value must have declined below 0.2 ng/ml prior to randomization
• Adequate hematologic, hepatic, and renal function:
• Hematologic
• Haemoglobin ≥9.0 g/dL independent of transfusions
• Neutrophils ≥1.5 Ths./µL
• Hepatic:
• Total bilirubin ≤1.5X upper limit of normal (ULN) \[except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN\]
• Alanine (ALT) and aspartate (AST) aminotransferase ≤2.5X ULN
• Renal:

You may not qualify if:

• Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone q.d.
• Prior cytotoxic chemotherapy or biologic therapy for the treatment of prostate Cancer.
• Prior or current treatment of prostate cancer with apalutamide, enzalutamide, darolutamide, or other investigational agents targeting the androgen receptor.
• Prior therapy with Sipuleucel-T or other vaccination or immunogenic therapy for the treatment of prostate Cancer.
• Prior treatment with abiraterone acetate or other androgen synthesis inhibitors (e. g. ketoconazole, TAK700, TOK001).
• Use of 5-α reductase inhibitors (eg, dutasteride, finasteride) ≤4 weeks prior to randomization.
• Prior surgical castration or medical castration using LHRH-Agonists or GnRH-Antagonists.
• Prior or current radiation or radionuclide (including radium-223 dichloride) therapy for treatment of prostate cancer (adjuvant radiation of the prostate bed without involvement of the regional lymph node template as by standard of care in case of positive surgical margins (R1) is allowed).
• Prior or current systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
• Any lymph node or distant metastasis.
• History of seizure or 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).
• Current or prior treatment with anti-epileptic medications for the treatment of seizures.
• Management of cardiovascular risk factors, such as hypertension, diabetes or dyslipidaemia should be optimised as per standard of care before treatment with apalutamide will be initiated
• Uncontrolled hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg. For patients with relevant comorbidities (e.g. diabetes) systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg). Patients with a history of hypertension are allowed provided that blood pressure is controlled by anti-hypertensive Treatment
• Patients with uncontrolled diabetes defined as HbA1c ≥7.5%

Sponsors & Collaborators

• Universität Münster: lead
• Janssen Pharmaceutica N.V., Belgium: collaborator

Study Sites (21)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

Location

Uniklinikum Salzburg, Landeskrankenhaus

Salzburg, 5020, Austria

Location

Hanusch-Krankenhaus

Vienna, 1140, Austria

Location

University Hospital Münster

Münster, North Rhine-Westfalia, 48149, Germany

Location

Universitätsklinikum Augsburg Klinik für Urologie

Augsburg, 86156, Germany

Location

GFO Kliniken Rhein-Berg

Bergisch Gladbach, 51465, Germany

Location

Urologische Partnerschaft Köln

Cologne, 50968, Germany

Location

Urologicum Duisburg

Duisburg, 47169, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

St. Antonius-Hospital Gronau GmbH Klinik für Urologie, Kinderurologie und Urologische Onkologie

Gronau, 48599, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

KLINIKUM LANDSHUT gemeinnützige GmbH

Landshut, 84034, Germany

Location

Klinikum Leverkusen gGmbH, Klinik für Urologie

Leverkusen, 51375, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, 23538, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Klinik für Urologie, Lehrstuhl Regensburg, Am Caritas Krankenhaus St. Josef

Regensburg, 93053, Germany

Location

UroGynZentrum

Wuppertal, 42103, Germany

Location

Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke

Wuppertal, 42283, Germany

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

Standard of Care; apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Martin Bögemann, Univ.-Prof. Dr. med.

  Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: March 4, 2020
• Study Start: December 10, 2020
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: June 20, 2024

Record last verified: 2024-06

Locations

AU (4); DE (17)