Neoadjuvant Degarelix With or Without Apalutamide (ARN-509) Followed by Radical Prostatectomy

NCT03080116 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: S588272016-002854-19
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Neoadjuvant hormonal therapy using luteinizing hormone releasing hormone (LHRH) agonists and/or anti-androgens has already demonstrated to downstage primary prostate cancer in patients treated by radical prostatectomy without a survival benefit. There is no evidence yet of a survival impact of LHRH antagonist (LHRHa) +/- new-generation anti-androgens in this setting. Thus novel studies are needed to assess this treatment combination. PURPOSE: To assess the difference in treatment antitumor effect between arms by measuring pathological tumor volume with minimal residual disease (MRD) following radical prostatectomy + pelvic lymph-node dissection (RP + PLND) for intermediate or high-risk prostate cancer patients.

Conditions

Prostate Cancer; Neoadjuvant Therapy; Androgen Antagonists; Prostatectomy

Keywords

Randomized; Placebo-controlled; Neoadjuvant; Androgen deprivation; Antiandrogen; Radical Prostatectomy

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease (MRD)

  Proportions of MRD between arms. MRD: tumor volume ≤ 0.25 cm3

  After 12 weeks of neoadjuvant therapy + RP + PLND

Secondary Outcomes (26)

• Difference in proportions of pathological downstage

  After 12 weeks of neoadjuvant therapy + RP + PLND

• Complete pathological response rates

  After 12 weeks of neoadjuvant therapy + RP + PLND

• Difference in proportions of patients with pN1 disease.

  After 12 weeks of neoadjuvant therapy + RP + PLND

• Proteins expression in prostatic tumour TMA's (tissue microarrays)

  After 12 weeks of neoadjuvant therapy + RP + PLND

• Transcriptome analysis by microarray expression platform

  At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND

Study Arms (2)

ARN-509 + degarelix

EXPERIMENTAL

Treatment period of 12 weeks before RP + PLND.

Drug: ARN-509; Drug: Degarelix

placebo + degarelix

ACTIVE COMPARATOR

Treatment period of 12 weeks before RP + PLND.

Drug: Degarelix; Other: Placebo

Interventions

ARN-509 DRUG

240mg/day (4x60mg tablets, Oral administration: OS)

Also known as: apalutamide

ARN-509 + degarelix

Degarelix DRUG

1st injection: 120mg Subcutaneous administration (SC) x2, 2nd-3rd SC injection 80mg monthly

ARN-509 + degarelix; placebo + degarelix

Placebo OTHER

4 tablets, per OS

placebo + degarelix

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
• Male aged 18 years or older (within 80 years)
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Diagnosis of intermediate (at least 2 of the following factors: cT2b, biopsy GS 7, PSA 10-20ng/ml) or high-risk prostatic adenocarcinoma (clinical stage≥T2c and/or biopsy GS≥8 and/or PSA\>20ng/ml), cN0-cN1, cM0.
• Patient amenable for open or robotic radical prostatectomy + pelvic lymph node dissection
• ECOG performance status: 0-1
• Adequate organ function as defined by the following criteria:
• White blood cells (WBC) ≥ 4.0 x109/L
• Platelet count ≥ 100 x109/L
• Hemoglobin ≥9 g/dl
• Creatinine ≤ 2 x ULN
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x upper limit of normality (ULN)
• Total serum bilirubin ≤1.5 x ULN.

You may not qualify if:

• Previous surgical/endoscopic treatments for prostatic disease
• Herbal and non-herbal products that in the opinion of the investigator may decrease PSA levels
• cM1 disease
• Any contraindication for PET or MR investigations
• History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Medications known to lower the seizure threshold
• History of:
• Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer currently in complete remission) within 5 years prior to randomization
• Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥100 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
• Gastrointestinal disorder affecting absorption
• Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Vlaams-brabant, 3000, Belgium

Location

Related Publications (1)

• Tosco L, Laenen A, Gevaert T, Salmon I, Decaestecker C, Davicioni E, Buerki C, Claessens F, Swinnen J, Goffin K, Oyen R, Everaerts W, Moris L, De Meerleer G, Haustermans K, Joniau S; P.E.A.R.L. (ProstatE cAncer Research Leuven). Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial. BMC Cancer. 2018 Apr 2;18(1):354. doi: 10.1186/s12885-018-4275-z.

  PMID: 29606109 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Steven Joniau

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: March 15, 2017
• Study Start: March 28, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Locations

BE (1)