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NCT03080116·Phase 2·INTERVENTIONAL

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

DegarelixOtherUnknown

Status

Unknown

Phase

Phase 2

Enrollment

90

Locations

1

Results

Not posted

Publications

1

Study summary

What the protocol is testing.

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.

Full detailed description

PRIMARY OBJECTIVE: To assess the difference in antitumor effect between the treatment arms by measuring MRD following radical prostatectomy. SECONDARY OBJECTIVES: To measure differences between study arms in * Proportions of post neoadjuvant prostate specific antigen (PSA) ≤ 0.3 ng/ml as a predictor of prostate cancer mortality * T down-staging, complete pathological response, PSA kinetics, Testosterone kinetics, operation time, blood loss, grade of surgical difficulty * New generation hybrid imaging 68Ga PSMA (Prostate-Specific Membrane Antigen) PET/MR (Positron emission tomography/Magnetic Resonance) derived parameters * Early biochemical recurrence as prognostic factor of prostate cancer mortality * Transcriptome and genome * Tissue microarrays (TMA) protein expression (DNA repair, resistance etc.) by immunohistochemistry * Perioperative safety and tolerability * Quality of life, erection recovery, continence through validated preoperative and postoperative questionnaires pre and postop (IEEF5, ICIQ, EORTC QLQ-C30) OUTLINE: interventional, single center, phase II, randomized, double blind, placebo controlled trial.

Interventions

Treatment arms and agents.

DRUG

ARN-509

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

DRUG

Degarelix

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

OTHER

Placebo

4 tablets, per OS

Timeline

From registration to results.

  1. First posted

    Mar 15, 2017

  2. Study start

    Mar 28, 2019

  3. Primary completion

    Jul 1, 2021

  4. Study completion

    Jul 1, 2024

  5. Results posted

    Not reported

  6. Registry updated

    Jul 3, 2024

Outcomes

What the study measures.

Primary outcomes

Minimal Residual Disease (MRD)

Time frame · After 12 weeks of neoadjuvant therapy + RP + PLND

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

Secondary outcomes

Difference in proportions of pathological downstage

Time frame · After 12 weeks of neoadjuvant therapy + RP + PLND

Any decrease in T stage from clinical to pathological stage

Complete pathological response rates

Time frame · After 12 weeks of neoadjuvant therapy + RP + PLND

Difference in proportions of complete pathological response (no evidence of tumour in the postoperative specimen) between arms.

Difference in proportions of patients with pN1 disease.

Time frame · After 12 weeks of neoadjuvant therapy + RP + PLND

Difference in proportions of lymph node invasion between arms

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

Time frame · After 12 weeks of neoadjuvant therapy + RP + PLND

Intensity of immunoreactivity and percentage of immunoreactive cells for, selected markers between arms. The TMA's will be produced from the formalin-fixed paraffin-embedded (FFPE) specimen of the RP.

Transcriptome analysis by microarray expression platform

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

To assess differences in the transcriptome in tumour tissue on formalin-fixed paraffin-embedded (FFPE) specimens: clinical-grade high-density oligonucleotide microarray expression platform and cloud-based informatics pipeline to interrogate 1.4M probe sets representing all known \~46K genes and non-coding RNAs.

Pathway profiling and Gene Set Enrichment Analyses

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

To assess differences in the transcriptome in tumour tissue on formalin-fixed paraffin-embedded (FFPE) specimens. Pathway profiling and Gene Set Enrichment Analyses will also be used to generate pathway scores for the 'androgen receptor signaling pathway'; determination of pathway scores for the DNA damage checkpoints and the different DNA repair pathways.

Genomic subtyping by exome-sequencing

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

Genomic subtyping (e.g., ERG, SPINK1, SPOP, FOXA1, PTEN, circulating nucleic acids (CNA) data...) will be performed based on exome-sequencing data. The exome and CNA data will be linked with the transcriptome data on androgen regulation and DNA repair pathways.

PSA kinetics

Time frame · Up to 40 months

Changes of PSA during time and comparison of PSA values and changes between arms.

Testosterone kinetics

Time frame · Up to 40 months

Comparison of total and free serum testosterone and testosterone change between arms

PSA nadir </=0.3ng/ml after neoadjuvant treatment

Time frame · After 12 weeks of neoadjuvant therapy before RP + PLND

Differences in proportions of PSA nadir \</=0.3ng/ml after neoadjuvant treatment. PSA nadir after neoadjuvant therapy and before external beam radiotherapy (EBRT) is an important biomarker of hormonal response and an independent prognostic factor of prostate cancer survival.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
80 Years
Sex
MALE
Healthy volunteers
No

Inclusion Criteria: 1. 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 2. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations 3. Male aged 18 years or older (within 80 years) 4. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features 5. 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. 6. Patient amenable for open or robotic radical prostatectomy + pelvic lymph node dissection 7. ECOG performance status: 0-1 8. 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. Exclusion Criteria: 1. Previous surgical/endoscopic treatments for prostatic disease 2. Herbal and non-herbal products that in the opinion of the investigator may decrease PSA levels 3. cM1 disease 4. Any contraindication for PET or MR investigations 5. 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) 6. Medications known to lower the seizure threshold 7. 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 8. Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.

Study locations

1 registered sites.

Belgium. Showing up to 24 locations stored in the fast local snapshot.

University Hospitals Leuven

Leuven, Vlaams-brabant, Belgium

Publications

Results and literature.

PMID 29606109 ↗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.

Primary links

Continue at the source.

ClinicalTrials.gov ↗Search PubMed ↗Search FDA ↗Search EMA ↗

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