Clinical trial • Phase III • Oncology
APALUTAMIDE for Castration-resistant prostate cancer
Phase III trial of APALUTAMIDE for Castration-resistant prostate cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Castration-resistant prostate cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 29-01-2024
- First CTIS Authorization Date
- 01-03-2024
Trial design
Randomised, placebo-controlled: apalutamide (jnj-56021927) versus apalutamide placebo. apalutamide information in product listing: max daily dose amount 240 mg (oral). background androgen deprivation therapy is continued. Phase III trial in Austria, Belgium, Poland and others.
- Randomised
- Yes
- Comparator
- Placebo-controlled: Apalutamide (JNJ-56021927) versus Apalutamide placebo. Apalutamide information in product listing: max daily dose amount 240 mg (oral). Background androgen deprivation therapy is continued.
- Target Sample Size
- 44
Eligibility
Recruits 44 Vulnerable population not selected; participants are adults (Age ≥ 18 years). Signed and dated informed consent is required: "Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to randomization"..
- Vulnerable Population
- Vulnerable population not selected; participants are adults (Age ≥ 18 years). Signed and dated informed consent is required: "Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to randomization".
Inclusion criteria
- {"criterion_text":"-1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as PSADT ≤ 10 months. PSADT is calculated using at least 3 PSA values obtained during continuous ADT (see Section 5.1)."}
- {"criterion_text":"-10. Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade 1 or baseline prior to randomization."}
- {"criterion_text":"-11. Adequate organ function as defined by the following criteria: -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 normal (ULN) -Total serum bilirubin ≤1.5 x ULN. Total serum bilirubin >1.5 x ULN is allowed if Gilbert's disease is documented prior to end of screening procedures -Serum creatinine ≤ 2 x ULN -Absolute neutrophil count (ANC) ≥ 1500/μL -Platelets ≥ 100,000/μL -Hemoglobin ≥ 9.0 g/dL -Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility."}
- {"criterion_text":"-12. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to randomization"}
- {"criterion_text":"-13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets, the completion of patient reported outcomes questionnaires and long-term follow-up visits"}
- {"criterion_text":"-2. Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL"}
- {"criterion_text":"-3. Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the patient is medically castrated, continuous dosing with GnRHa must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone."}
- {"criterion_text":"-4.Patients receiving bone loss prevention treatment with bone-sparing agents indicated for the treatment of osteoporosis at doses and dosing schedule appropriate for the treatment of osteoporosis (e.g., denosumab [Prolia®], zoledronic acid [Reclast®]) must be on stable doses for at least 4 weeks prior to randomization."}
- {"criterion_text":"-5. Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout."}
- {"criterion_text":"-6. At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors (e.g., dutasteride, finasteride), estrogens (irrespective of dose used), and any other anti-cancer therapy prior to randomization, including chemotherapy given in the adjuvant/neoadjuvant setting (e.g.,clinical trial)"}
- {"criterion_text":"-7. At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization"}
- {"criterion_text":"-8. Age ≥ 18 years"}
- {"criterion_text":"-9. Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1."}
Exclusion criteria
- {"criterion_text":"-1. Presence of distant metastases confirmed by blinded independent central review (BICR), including CNS and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes <2 cm in short axis (N1) located below the iliac bifurcation are allowed"}
- {"criterion_text":"-2. Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis due to primary tumor (e.g., tumor obstruction of bladder trigone)"}
- {"criterion_text":"-3. Prior treatment with second generation anti-androgens (e.g., enzalutamide)"}
- {"criterion_text":"-4. Prior treatment with CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide)"}
- {"criterion_text":"-5. Prior treatment with radiopharmaceutical agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other investigational agent for NM-CRPC"}
- {"criterion_text":"-6. Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting"}
- {"criterion_text":"-7. History of seizure or condition that may pre-dispose to seizure (e.g., 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)"}
- {"criterion_text":"-8. Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 4 weeks prior to randomization): Medications known to lower the seizure threshold (for a complete list please see Appendix 5) Herbal (e.g. saw palmetto) and non-herbal (e.g. pomegranate) products that may decrease PSA levels Systemic (oral/IV/IM) corticosteroids. Short term use (≤ 4 weeks) of corticosteroids during the study is allowed if clinically indicated, but it should be tapered off as soon as possible Any other experimental treatment on another clinical trial Agents indicated for the prevention of skeletal-related events in patients with solid tumors (e.g., denosumab [Xgeva®])"}
- {"criterion_text":"-9. 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 randomization Any of the following within 6 months 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 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 antihypertensive treatment. Gastrointestinal disorder affecting absorption Active infection, such as human immunodeficiency virus (HIV) Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures."}
Endpoints
Primary endpoints
- {"endpoint_text":"-Metastasis-Free Survival (MFS)","definition_or_measurement_approach":"To demonstrate superiority in the metastasis-free survival (MFS) of men with high risk NM-CRPC treated with Apalutamide versus placebo"}
Secondary endpoints
- {"endpoint_text":"-Time to Metastasis (TTM)","definition_or_measurement_approach":"Hierarchical testing will be performed for the secondary endpoints in the prespecified order."}
- {"endpoint_text":"-Progression-Free Survival (PFS)","definition_or_measurement_approach":"Hierarchical testing will be performed for the secondary endpoints in the prespecified order."}
- {"endpoint_text":"-Time to symptomatic progression","definition_or_measurement_approach":"Hierarchical testing will be performed for the secondary endpoints in the prespecified order."}
- {"endpoint_text":"-Overall Survival (OS)","definition_or_measurement_approach":"Hierarchical testing will be performed for the secondary endpoints in the prespecified order."}
- {"endpoint_text":"-Time to initiation of cytotoxic chemotherapy","definition_or_measurement_approach":"Hierarchical testing will be performed for the secondary endpoints in the prespecified order."}
Recruitment
- Planned Sample Size
- 44
- Recruitment Window Months
- 163
- Consent Approach
- Signed and dated informed consent document required from the patient (or legally acceptable representative) prior to randomization. Participants are adults (Age ≥ 18 years) so no assent process for minors. Subject information and informed consent form documents are available (example: L1_ES_SIS-ICF_Adult_Spanish_redacted).
Geography
- Total Number Of Sites
- 24
- Total Number Of Participants
- 30
Austria
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 26-08-2024
- Processing Time Days
- 189
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- University Hospital Graz
- Department Name
- Universitätsklinik für Urologie
- Principal Investigator Name
- Georg Hutterer
- Principal Investigator Email
- georg.hutterer@medunigraz.at
- Contact Person Name
- Georg Hutterer
- Contact Person Email
- georg.hutterer@medunigraz.at
Belgium
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 23-08-2024
- Processing Time Days
- 186
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Department of Urology
- Principal Investigator Name
- Nicolaas Lumen
- Principal Investigator Email
- nicolaas.lumen@uzgent.be
- Contact Person Name
- Nicolaas Lumen
- Contact Person Email
- nicolaas.lumen@uzgent.be
Poland
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 27-08-2024
- Processing Time Days
- 190
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Wielkopolskie Centrum Onkologii Im. Marii Sklodowskiej-Curie
- Department Name
- Oddzial Radioterapii
- Principal Investigator Name
- Piotr Milecki
- Principal Investigator Email
- piotr.milecki@wco.pl
- Contact Person Name
- Piotr Milecki
- Contact Person Email
- piotr.milecki@wco.pl
- Site Name
- Specjalista Sp. z o.o.
- Department Name
- Oddzial onkologyczny
- Principal Investigator Name
- Piotr Humanski
- Principal Investigator Email
- specjalista@post.pl
- Contact Person Name
- Piotr Humanski
- Contact Person Email
- specjalista@post.pl
France
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 28-08-2024
- Processing Time Days
- 191
- Number Of Sites
- 3
- Number Of Participants
- 1
Sites
- Site Name
- Pellegrin Hospital
- Department Name
- Department of Urology
- Principal Investigator Name
- Grégoire Robert
- Principal Investigator Email
- gregoire.robert@chu-bordeaux.fr
- Contact Person Name
- Grégoire Robert
- Contact Person Email
- gregoire.robert@chu-bordeaux.fr
- Site Name
- Centre Jean Perrin
- Department Name
- Department of Urology
- Principal Investigator Name
- Hakim Mahammedi
- Principal Investigator Email
- hakim.mahammedi@clermont.unicancer.fr
- Contact Person Name
- Hakim Mahammedi
- Contact Person Email
- hakim.mahammedi@clermont.unicancer.fr
- Site Name
- Centre Antoine Lacassagne
- Department Name
- Department of Urology
- Principal Investigator Name
- Jean-Marc Ferrero
- Principal Investigator Email
- jean-marc.ferrero@nice.unicancer.fr
- Contact Person Name
- Jean-Marc Ferrero
- Contact Person Email
- jean-marc.ferrero@nice.unicancer.fr
Romania
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 28-08-2024
- Processing Time Days
- 191
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Policlinica De Diagnostic Rapid S.A.
- Department Name
- Oncologie Medicala
- Principal Investigator Name
- Daniel Ciurescu
- Principal Investigator Email
- ciurescu@yahoo.com
- Contact Person Name
- Daniel Ciurescu
- Contact Person Email
- ciurescu@yahoo.com
Slovakia
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 23-08-2024
- Processing Time Days
- 186
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Cuimed s.r.o.
- Department Name
- Urológia
- Principal Investigator Name
- Frederico Goncalves
- Principal Investigator Email
- cuimed1@gmail.com
- Contact Person Name
- Frederico Goncalves
- Contact Person Email
- cuimed1@gmail.com
Netherlands
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 23-08-2024
- Processing Time Days
- 186
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Sint Franciscus Vlietland Groep Stichting
- Department Name
- Oncologie Centrum
- Principal Investigator Name
- Paul Hamberg
- Principal Investigator Email
- p.hamberg@franciscus.nl
- Contact Person Name
- Paul Hamberg
- Contact Person Email
- p.hamberg@franciscus.nl
- Site Name
- Noordwest Ziekenhuisgroep Stichting
- Department Name
- Afdelingen Urologie
- Principal Investigator Name
- Ton A. Roeleveld
- Principal Investigator Email
- t.a.roeleveld@nwz.nl
- Contact Person Name
- Ton A. Roeleveld
- Contact Person Email
- t.a.roeleveld@nwz.nl
- Site Name
- Spaarne Gasthuis
- Department Name
- Oncologie Centrum
- Principal Investigator Name
- Aart Beeker
- Principal Investigator Email
- abeeker@spaarneziekenhuis.nl
- Contact Person Name
- Aart Beeker
- Contact Person Email
- abeeker@spaarneziekenhuis.nl
Denmark
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 23-08-2024
- Processing Time Days
- 186
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Rigshospitalet
- Department Name
- CPH Prostate Cancer Center, Department of Urology
- Principal Investigator Name
- Klaus Brasso
- Principal Investigator Email
- klaus.brasso@regionh.dk
- Contact Person Name
- Klaus Brasso
- Contact Person Email
- klaus.brasso@regionh.dk
Czechia
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 28-08-2024
- Processing Time Days
- 191
- Number Of Sites
- 2
- Number Of Participants
- 5
Sites
- Site Name
- Urocentrum Praha s.r.o.
- Department Name
- Urocentrum Praha S.r.o.
- Principal Investigator Name
- Michaela Matoušková
- Principal Investigator Email
- matouskova@urocentrum.cz
- Contact Person Name
- Michaela Matoušková
- Contact Person Email
- matouskova@urocentrum.cz
- Site Name
- Vseobecna Fakultni Nemocnice V Praze
- Department Name
- Urologická klinika VFN a 1. LF UK v Praze
- Principal Investigator Name
- Ivan Pavlík
- Principal Investigator Email
- ivan.pavlik@vfn.cz
- Contact Person Name
- Ivan Pavlík
- Contact Person Email
- ivan.pavlik@vfn.cz
Italy
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 26-08-2024
- Processing Time Days
- 189
- Number Of Sites
- 3
- Number Of Participants
- 3
Sites
- Site Name
- Azienda Ospedaliero-Universitaria Maggiore Della Carita
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Alessia Mennitto
- Principal Investigator Email
- alessia.mennitto@maggioreosp.novara.it
- Contact Person Name
- Alessia Mennitto
- Contact Person Email
- alessia.mennitto@maggioreosp.novara.it
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- S.C. Oncologia Medica I
- Principal Investigator Name
- Roberto Filippi
- Principal Investigator Email
- rfilippi@cittadellasalute.to.it
- Contact Person Name
- Roberto Filippi
- Contact Person Email
- rfilippi@cittadellasalute.to.it
- Site Name
- European Institute Of Oncology S.r.l.
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Franco Nolé
- Principal Investigator Email
- franco.nole@ieo.it
- Contact Person Name
- Franco Nolé
- Contact Person Email
- franco.nole@ieo.it
Germany
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 26-08-2024
- Processing Time Days
- 189
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- Universitaetsklinikum Muenster AöR
- Department Name
- Department of Urology and Children Urology at University Hospital Muenster
- Principal Investigator Name
- Martin Boegemann
- Principal Investigator Email
- martin.boegemann@ukmuenster.de
- Contact Person Name
- Martin Boegemann
- Contact Person Email
- martin.boegemann@ukmuenster.de
- Site Name
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Department Name
- Department of Urology and Pediatric Urology at University of Mainz
- Principal Investigator Name
- Anita Thomas
- Principal Investigator Email
- anita.thomas@unimedizinmainz.de
- Contact Person Name
- Anita Thomas
- Contact Person Email
- anita.thomas@unimedizinmainz.de
Spain
- Earliest CTIS Part Ii Submission Date
- 19-02-2024
- Latest Decision Or Authorization Date
- 09-12-2025
- Processing Time Days
- 659
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Consorcio Hospitalario Provincial De Castellon
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Carlos Ferrer Albiach
- Principal Investigator Email
- ferreralbiach@gmail.com
- Contact Person Name
- Carlos Ferrer Albiach
- Contact Person Email
- ferreralbiach@gmail.com
- Site Name
- Parc Tauli Hospital Universitari
- Department Name
- Servicio de Urología
- Principal Investigator Name
- Enrique Gallardo Díaz
- Principal Investigator Email
- egallardo@tauli.cat
- Contact Person Name
- Enrique Gallardo Díaz
- Contact Person Email
- egallardo@tauli.cat
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Joaquin Mateo Valderrama
- Principal Investigator Email
- jmateo@vhio.net
- Contact Person Name
- Joaquin Mateo Valderrama
- Contact Person Email
- jmateo@vhio.net
Sponsor
Primary sponsor
- Full Name
- Aragon Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Perceptive Eclinical Limited
- Responsibilities
- sponsorDuties codes: 14, 15 (IP returns and destruction), 3
- Name
- Icon Clinical Research Limited
- Responsibilities
- sponsorDuties codes: 5
- Name
- Almac Clinical Services Limited
- Responsibilities
- sponsorDuties codes: 15 (IP returns and destruction)
Third parties
- {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"sponsorDuties codes: 14, 15 (IP returns and destruction), 3","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 5","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: 15 (IP returns and destruction)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- JNJ-56021927
- Active Substance
- APALUTAMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- prodAuthStatus: 1
- Maximum Dose
- 240 mg
- Investigational Product Name
- Apalutamide placebo
- Combination Treatment
- Yes
Related trials
Other published trials that may interest you.
- GDC-9545 for Locally advanced or metastatic estrogen receptor-positive breast cancer
- Abemaciclib for Stage IV lung cancer | Breast cancer
- BGB-43395 for Advanced or metastatic solid tumors | Hormone receptor positive HER2 negative breast cancer
- AZD9833 for Estrogen receptor-positive HER2-negative advanced breast cancer
- Pembrolizumab for Classical Hodgkin lymphoma | Melanoma | Solid tumours (MSI-H/dMMR) | Solid tumours (TMB-H)