Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Niraparib

Docetaxel

Abiraterone Acetate

Prednisone

Atezolizumab

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

LHRHa plus apalutamide plus abiraterone acetate plus prednisone.

LHRHa plus abiraterone acetate plus prednisone.

LHRHa plus abiraterone acetate plus prednisone plus docetaxel.

LHRHa plus abiraterone acetate plus prednisone plus niraparib

4 tablets by mouth once a day for 24 weeks

Apalutamide 60mg Tab

4 tablets by mouth on an empty stomach once a day for 16 weeks

Abiraterone Acetate 250mg

1 tablet by mouth once daily while taking abiraterone acetate

Prednisone 5mg Tab

Infusion every 3 weeks for 6 cycles (each cycle has 3 weeks)

3 capsules by mouth once daily for 16 weeks

Niraparib 100mg Oral Capsule

1200mg infusion every 3 weeks for 6 cycles

Martin E Gleave, MD

Miran Kenk, PhD

Anthony Martinez

Marc Dall'Era, MD

Mamta Parikh, MD

Daniella Furtado

Adam Kibel, MD

Lindsay Sazkaly

Todd Morgan, MD

askMDAnderson

Brian Chapin, M.D.

Jonathan Ma

Pascale Juneau

Rodney Breau, MD

Anuja Parikh, HBSc

Neil Fleshner, M.D.

The objective of this study is to see if providing an appropriate therapy based on the genomic testing of prostate tumour tissue will result in an improved clinical response.

Each participant will be treated with 8 weeks of a luteinizing hormone-releasing hormone agonist (LHRHa) plus apalutamide (APA) while genome sequence characterization is being done. Participants with biopsy specimens deemed unevaluable for genomic testing will remain on LHRHa plus APA for an additional 16 weeks.

Participants with evaluable tissue will be assigned to one of the open-label sub-studies on the basis of genomic profiling results. Within each group, they will be randomized to a specific treatment arm either LHRHa plus APA alone or adding abiraterone acetate and prednisone, docetaxel or niraparib.

The study will evaluate the response rate and outcomes after radical prostatectomy in each arm of the trial.

This is a multi-centre adaptive multi-arm phase II study. Participants are treated with an induction period of at least 8 weeks of LHRH agonist/antagonist (LHRHa) plus apalutamide (APA) while genome sequence characterization is being done.

Genomic sequencing analysis will be performed centrally by Tempus, a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory. For the DNA gene profiling, formalin-fixed paraffin-embedded (FFPE) prostate cancer and surrounding healthy tissue from diagnostic biopsies will be used for genetic analysis. Copy number profiling will be performed using array Comparative Genomic Hybridisation (aCGH). Targeted sequencing using MiSeq (Illumina) and Ion Proton (Life Technologies) platforms will be performed to identify mutations in a panel of 648 genes.

Based on previous studies, we conservatively expect up to 25% of unevaluable needle biopsy specimens with inadequate/insufficient tumor tissue for genome sequencing. The patients with unevaluable tissue will continue on the master protocol (LHRHa + APA) for an additional 16 weeks followed by radical prostatectomy.

The genomically evaluable patients will be assigned to a specific sub-protocol according to the results of the genomic profile and randomized to a treatment arm within the sub-protocol for 16 weeks, with additional inclusion and exclusion criteria specified in dedicated sub-protocols. Radical prostatectomy will follow sub-protocol treatment.

Sub-protocol 1 - AR axis: No targetable actionable aberration; presence of TMPRSS2-ERG fusion, CHD1 loss or SPOP mutations: (\~50% expected prevalence in study population) randomized to:

1. LHRHa + APA for 16 weeks or
2. LHRHa + APA + AAP (Abiraterone Acetate + Prednisone) for 16 weeks

Sub-protocol 2 - Loss of tumour suppressor genes - PTEN, TP53 or TB loss (\~40%, bad prognosis) randomized to:

1. LHRHa + AAP for 16 weeks or
2. LHRHa + AAP + docetaxel for 6 cycles

Sub-protocol 3 - DNA damage response alterations (e.g. BRCA1/2, ATM, FANCONI, CDK12) in 6-8% assigned to:

* LHRHa + AAP + PARP (Poly \[ADP-ribose\] polymerase) inhibitors (niraparib) for 16 weeks

Sub-protocol 4 - Hypermutation, microsatellite instability (MSI), Lynch syndrome or CDK12 in less than 5% assigned to:

a. LHRHa + APA plus PD-L1 inhibitor (atezolizumab) for 16 weeks

Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer

Pathological Minimal Residual Disease (pMRD): pathological minimal residual disease (pMRD) is defined as residual tumour 5mm or less.

Pathological minimal residual disease is defined as residual tumour 5 mm or less.

The Brief Pain Inventory-Short Form (BPI-SF) is a 9-item, self administered questionnaire which evaluates the severity of a participant's level of pain and impact on daily functioning. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks), as well as the End of Treatment (EoT) visit.

The EQ-5D-5L is a widely used instrument developed in Europe to evaluate the generic quality of life. The EQ-5D-5L has two components: the EQ-5D descriptive system and the EQ visual analogue scale. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks) as well as at the EoT visit.

This will be measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. The FACT-P is a multidimensional, self-report QoL instrument specifically designed for use with patients who have prostate cancer. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks) as well as at the EoT visit.

Janssen Inc.

University Health Network, Toronto

University of British Columbia

Principal Investigator/Study Chair

Symptoms and General Pathology

Recurrence

Disease Attributes

Androgens

Apalutamide (240 mg once daily) in combination with ADT for 12 cycles (28 days of each cycle)

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

The choice of ADT will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.

Androgen deprivation therapy(ADT)

Hongqian Guo, PhD

Luwei Xu

Shun Zhang, PhD

Xuefeng Qiu, PhD

Xiaolin Wang

ARES is a multicenter, single-arm, phase 2 trial to evaluate the efficacy and safety of ADT in combination with apalutamide as an adjuvant regimen for patients with high risk of recurrence after radical prostatectomy.

Adjutant Apalutamide Plus ADT in Post-RP Patients With High Risk of Recurrence (ARES Study)

Adjuvant Androgen Deprivation Therapy Combined With Apalutamide for Prostate Cancer Patients Post Radical-prostatectomy With High-risk of Reoccurrence: a Prospective, Single-arm, Multicenter Trial (ARES Study)

It is defined as the proportion of patients without biochemical progression or death 2 year after initiation with Apalutamide plus ADT.

Biochemical progression is defined as an increase of more than 0.5 ng/mL from PSA nadir after treatment (confirmed rise on at least two separate occasions) or any evidence of clinical relapse/metastasis or the initiation of any anti-prostate cancer therapy or death due to any cause.

It is defined as the proportion of patients without biochemical recurrence or any evidence of clinical relapse/metastasis or initiation of any other anti-prostate cancer therapy or death due to any cause.

It is defined as the time from the initiation of treatment to the first occurrence of biochemical recurrence, and the definition of biochemical progression is the same as that of the primary observation endpoint;

It is defined as the time from the start of treatment to the first occurrence of distant metastasis or death, whichever occurs first; distant metastasis can be diagnosed by imaging results or pathology by Blinded Independent Central Review (BICR);

The FACT-P scale (39 items) includes a Functional Assessment of Cancer Therapy - General (FACT-G, which consists of 4 subscales measuring physical, functional, social/family, and emotional well-being) and a specific subscale for prostate cancer. The total score is calculated by summing the scores of FACT-G and the prostate cancer subscales, ranging from 0 to 156, with higher scores indicating better functional status

It is defined as the proportion of patients with testosterone recovery 2 year after initiation of apalutamide plus ADT. Testosterone recovery is defined as testosterone level \>50 ng/dL.

Testosterone recovery is defined as testosterone level \>50 ng/dL

All adverse events (AEs) are assessed and graded according to NCI-CTCAE v5.0. Safety will be assessed and documented after the initiation of study drug, regardless of relationship to the study drug, until 30 days after the last study treatment or the initiation of new antineoplastic therapy, whichever occurs first.

Xian-Janssen Pharmaceutical Ltd.

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Chief physician of Department of Urology

Adenocarcinoma

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

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

Standard of care

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

Apalutamide 60Mg Tab

Martin Bögemann, Univ.-Prof. Dr. med.

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).

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

A Randomized, Open-label, Phase 2 Study of Adjuvant Apalutamide or Standard of Care in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy

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.

In case of a BCR, PSA kinetics as the PSADT are calculated based on the monthly PSA measurements during the first six months after the BCR. The values used to determine the BCR are included in the calculation of PSA kinetics as well.

PSADT is calculated according to Pound et al. by the natural log of 2 (0.693) divided by the slope of the relationship between the log of PSA and time of PSA measurement (i.e. time from BCR) for each patient \[33\]. PSADT can also be assessed using the MSKCC PSADT calculator (https://www.mskcc.org/nomograms/prostate/psa_doubling_time) using the above definitions.

Safety and tolerability assessed on the basis of adverse events, more precisely adverse events, serious adverse events, adverse reactions, and serious adverse reactions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer	NCT04812366	Prostate Cancer	Apalutamide 60m... Abiraterone Ace... Prednisone 5mg ... Docetaxel Niraparib 100mg... Atezolizumab	18 Years -	University of British Columbia
Adjutant Apalutamide Plus ADT in Post-RP Patients With High Risk of Recurrence (ARES Study)	NCT05778097	Prostate Cancer Biochemical Rec... High Risk	Apalutamide 60m... Androgen depriv...	18 Years - 75 Years	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Adjuvant Apalutamide in Subjects With High-risk Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy	NCT04295447	Prostatic Neopl...	Standard of car... Apalutamide 60M...	18 Years -	Universität Münster
Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer	NCT04812366	Prostate Cancer	Apalutamide 60m... Abiraterone Ace... Prednisone 5mg ... Docetaxel Niraparib 100mg... Atezolizumab	18 Years -	University of British Columbia
Adjutant Apalutamide Plus ADT in Post-RP Patients With High Risk of Recurrence (ARES Study)	NCT05778097	Prostate Cancer Biochemical Rec... High Risk	Apalutamide 60m... Androgen depriv...	18 Years - 75 Years	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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