Clinical trial • Phase III • Oncology

CAPIVASERTIB for Metastatic hormone-sensitive prostate cancer (PTEN deficiency)

Phase III trial of CAPIVASERTIB for Metastatic hormone-sensitive prostate cancer (PTEN deficiency).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic hormone-sensitive prostate cancer (PTEN deficiency)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
07-05-2024
First CTIS Authorization Date
21-06-2024

Trial design

Randomised, placebo + abiraterone versus capivasertib + abiraterone (no doses/schedules specified in ctis record)-controlled Phase III trial in France, Spain, Czechia and others.

Randomised
Yes
Comparator
Placebo + Abiraterone versus Capivasertib + Abiraterone (no doses/schedules specified in CTIS record)
Biomarker Stratified
True, biomarker: PTEN deficiency (centralised PTEN IHC)
Target Sample Size
741

Eligibility

Recruits 741 No vulnerable population selected. Trial enrols adult male patients only; informed consent required from participants. Separate subject information and informed consent forms and addenda exist for biomarker testing, genetic research and pregnant partners (country-specific ICFs available). No paediatric consent/assent provisions (not applicable)..

Vulnerable Population
No vulnerable population selected. Trial enrols adult male patients only; informed consent required from participants. Separate subject information and informed consent forms and addenda exist for biomarker testing, genetic research and pregnant partners (country-specific ICFs available). No paediatric consent/assent provisions (not applicable).

Inclusion criteria

  • {"criterion_text":"- 1. Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic hormone-sensitive prostate adenocarcinoma without small cell tumours\n- 2. Consent to provide a FFPE tissue block (preferred) or slides. Tissue from bone metastases is not acceptable\n- 3. A valid PTEN IHC result indicating PTEN deficiency (centralized testing)\n- 4. Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion accurately assessed at baseline and suitable for repeated assessment with CT and/or MRI. PSMA PET identification only will not be eligible\n- 5. Candidate for abiraterone and steroid therapy\n- 6. Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral orchiectomy\n- 7. Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks\n- 8. Able and willing to swallow and retain oral medication\n- 9. 7 day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory(BFI) questionnaires and the analgesic diary during screening completed\n- 10. Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm"}

Exclusion criteria

  • {"criterion_text":"- 1.Prior radical prostatectomy or definitive radiotherapy (RT) with therapeutic intent for prostate cancer. Palliative RT is allowed within 4 wks before start of study \n- 2.Major surgery within 4 wks of start of study \n- 3.Brain metastases, or spinal cord compression (unless asymptomatic, treated and stable \n- 4 Past medical history or evidence of ongoing interstitial lung disease or radiation pneumonitis requiring steroids \n- 5.Any of the following cardiac criteria: -Mean resting QTc >470 msec -History of QT prolongation associated with other medications that required discontinuation - Family history of long QT syndrome or unexplained sudden death under the age of 40 - Medical history significant for arrhythmia, symptomatic or requiring treatment; symptomatic or uncontrolled atrial fibrillation; or asymptomatic sustained ventricular tachycardia - Any clinically important abnormalities of resting ECG - Factors that increase the risk of QTc prolongation or of arrhythmic events, or any concomitant medication known to significantly prolong the QT interval and associated with Torsade de Pointes - Experience of any of the following in the preceding 3 months: coronary artery bypass graft, angioplasty, myocardial infarction or unstable angina pectoris - Congestive heart failure NYHA Grade ≥2 - Symptomatic hypotension (SBP<90 mmHg and/or DBP<50mmHg)or uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥95 mmHg) \n- 6. Any of following clinically significant abnormalities of glucose metabolism: - Patients with diabetes mellitus type 1 or 2 requiring insulin - HbA1c ≥8.0% (63.9 mmol/mol) \n- 7. Inadequate bone marrow reserve or organ function: - Neutrophils <1.5x109/L - Platelets <100x109/L - Hb <9g/dL (<5.59 mmol/L) - ALT and AST >2.5x ULN if no liver metastases or >5x ULN if liver metastases - Bilirubin >1.5x ULN - CrCL <50 mL/min \n- 8. Severe or uncontrolled systemic diseases, including active bleeding diatheses, active infection including hepatitis B and C. diagnosis with HIV or a history of an AIDS opportunistic infection within the past 12 months \n- 9. Unevaluable for both bone and soft tissue progression as defined by the following : bone \"superscan\" and no soft tissue lesion evaluable by RECIST \n- 10.Conditions that would preclude adequate absorption of capivasertib\n- 11. Any other clinical finding that, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug\n- 12. Evidence of dementia, altered mental status, or any psychiatric condition prohibiting understanding or rendering of informed consent\n- 13. Previous allogeneic bone marrow or solid organ transplant \n- 14. History of another primary malignancy except for malignancy treated with curative intent with no known disease ≥ 2 years before starting study and of low recurrence risk \n- 15. Following treatments: - Nitrosourea or mitomycin C within 6 wks of the start of study - Any other anticancer therapy or immunosuppressant medication (other than corticosteroids) within 3 wks of the start of study - Strong inhibitors or inducers of CYP3A4 within 2 wks before the start of study - Drugs known to prolong the QT interval and associated with torsades de pointes within 5 T½of the start of the study \n- 16. Participation in another clinical study with an investigational product administered in the last 30 days or 5 half-lives whichever is longer \n- 17. History of hypersensitivity to active or inactive excipients of capivasertib, abiraterone, or drugs with a similar chemical structure or class \n- 18. Involvement in the planning and/or conduct of the study \n- 19. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study requirements \n- 20. Any restriction or contraindication based on the local prescribing information that would prohibit the use of abiraterone"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1.Radiographic Progression-free Survival (rPFS) in patients with PTENdeficient Per Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST 1.1) for soft tissue and/or Prostate Cancer Working Group 3(PCWG3) for bone as Assessed by the Investigator","definition_or_measurement_approach":"Assessment by the investigator of radiographic progression-free survival (rPFS) using RECIST v1.1 for soft tissue lesions and PCWG3 criteria for bone lesions."}

Secondary endpoints

  • {"endpoint_text":"- 1.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of overall survival","definition_or_measurement_approach":"Assessment of overall survival (time from randomisation to death from any cause) as a comparison between treatment arms."}
  • {"endpoint_text":"- 2.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start of first subsequent therapy or death (TFST)","definition_or_measurement_approach":"Time to start of first subsequent therapy or death (TFST) as assessed for each participant."}
  • {"endpoint_text":"- 3.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start symptomatic skeletal event-free survival (SSE-FS)","definition_or_measurement_approach":"Time until symptomatic skeletal event or death (SSE-FS) compared between arms."}
  • {"endpoint_text":"- 4.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to pain progression (TTPP)","definition_or_measurement_approach":"Time to pain progression (TTPP) as measured by patient-reported assessments and analgesic diary/questionnaires."}
  • {"endpoint_text":"- 5.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to PSA progression","definition_or_measurement_approach":"Time to PSA progression as defined by protocol-specified PSA criteria."}
  • {"endpoint_text":"- 6.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of progression-free survival after next-line treatment (PFS2) 7.To evaluate the PK of capivasertib in combination with abiraterone","definition_or_measurement_approach":"PFS2: progression-free survival after next-line treatment; PK: pharmacokinetic evaluation of capivasertib when combined with abiraterone."}

Recruitment

Planned Sample Size
741
Recruitment Window Months
34
Consent Approach
Informed consent is obtained from adult participants. Subject Information Sheets and Informed Consent Forms are available in multiple country-specific versions (examples in CTIS: English, French, Spanish, Polish, Dutch, Slovak, Bulgarian). Separate ICFs/addenda exist for biomarker status determination, genetic research, pregnant partners and handling personal data. No paediatric assent procedures (adults only).

Geography

Total Number Of Sites
65
Total Number Of Participants
271

France

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
03-03-2026
Processing Time Days
642
Number Of Sites
12
Number Of Participants
38

Sites

Site Name
Institut Bergonie
Department Name
Oncology
Contact Person Name
Guilhem ROUBAUD
Site Name
Hospices Civils De Lyon
Department Name
Oncology
Contact Person Name
Sophie TARTAS
Contact Person Email
sophie.tartas@chu-lyon.fr
Site Name
Besancon University Hospital Center
Department Name
Oncology
Contact Person Name
Tristan MAURINA
Contact Person Email
t1maurina@chu-besancon.fr
Site Name
Institut Regional Du Cancer De Montpellier
Department Name
Oncology
Contact Person Name
Diego TOSI
Contact Person Email
Diego.Tosi@icm.unicancer.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncology
Contact Person Name
Philippe BARTHELEMY
Contact Person Email
p.barthelemy@icans.eu
Site Name
Institut Mutualiste Montsouris
Department Name
Oncology
Contact Person Name
Raphael COLLE
Contact Person Email
raphael.colle@imm.fr
Site Name
Institut Paoli Calmettes
Department Name
Oncology
Contact Person Name
Gwenaelle GRAVIS
Contact Person Email
GRAVISG@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Urology
Contact Person Name
Romain MATHIEU
Contact Person Email
romain.MATHIEU@chu-rennes.fr
Site Name
Centre Hospitalier Intercommunal De Cornouaille
Department Name
Oncology
Contact Person Name
Josselin ANNIC
Site Name
Hospital Foch
Department Name
Oncology
Contact Person Name
Raffaele RATTA
Contact Person Email
r.ratta@hopital-foch.com
Site Name
Centre Antoine Lacassagne
Department Name
Oncology
Contact Person Name
Delphine BORCHIELLINI
Site Name
Institut Gustave Roussy
Department Name
Oncology
Contact Person Name
Alice BERNARD-TESSIER

Spain

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
04-03-2026
Processing Time Days
643
Number Of Sites
10
Number Of Participants
69

Sites

Site Name
Hospital Clinico San Carlos
Department Name
Oncology
Contact Person Name
Javier Puente Vazquez
Contact Person Email
javier.puente@salud.madrid.org
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Oncology
Contact Person Name
Jose Pablo Maroto Rey
Contact Person Email
JMaroto@santpau.cat
Site Name
Hospital Universitario Central De Asturias
Department Name
Oncology
Contact Person Name
Carlos Alvarez Fernandez
Contact Person Email
carlos.alvfer@gmail.com
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Oncology
Contact Person Name
Ignacio Duran Martinez
Contact Person Email
ignacioduranmartinez@gmail.com
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Oncology
Contact Person Name
Alberto Sanchez Camacho Mejias
Contact Person Email
sanchezmejias@hotmail.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncology
Contact Person Name
Teresa Alonso Gordoa
Contact Person Email
talonsogordoa@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology
Contact Person Name
Jose Angel Arranz Arija
Contact Person Email
jarranza.oncomed@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncology
Contact Person Name
Alberto Font Pous
Contact Person Email
afont@iconcologia.net
Site Name
Complejo Hospitalario Universitario Insular Materno Infantil
Department Name
Oncology
Contact Person Name
Alfonso Gomez de Liaño Lista
Contact Person Email
agomezdeliano84@gmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Daniel Castellano Gauna
Contact Person Email
cdanicas@hotmail.com

Czechia

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
641
Number Of Sites
6
Number Of Participants
13

Sites

Site Name
Urocentrum Praha s.r.o.
Contact Person Name
Michaela Matouskova
Contact Person Email
matouskova@urocentrum.cz
Site Name
Fakultni Nemocnice Bulovka
Department Name
Ustav Radiacni Onkologie
Contact Person Name
Petra Holeckova
Contact Person Email
petra.holeckova@bulovka.cz
Site Name
Fakultni Nemocnice U Sv Anny V Brne
Department Name
Onkologicko-chirurgicke oddeleni
Contact Person Name
Jana Katolicka
Contact Person Email
jana.katolicka@fnusa.cz
Site Name
Fakultni Nemocnice Kralovske Vinohrady
Department Name
Radioterapeuticka a onkologicka klinika
Contact Person Name
Jan Dvorak
Contact Person Email
jan.dvorak@fnkv.cz
Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
Klinika onkologie a radioterapie
Contact Person Name
Jiri Petera
Contact Person Email
jiri.petera@fnhk.cz
Site Name
NH Hospital a.s.
Department Name
Onkologicke oddeleni
Contact Person Name
Martin Smakal
Contact Person Email
msmakal@gmail.com

Belgium

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
641
Number Of Sites
4
Number Of Participants
20

Sites

Site Name
Az Maria Middelares Gent
Department Name
Medical Oncology
Contact Person Name
Christof Vulsteke
Site Name
Universitair Ziekenhuis Gent
Department Name
Urologie
Contact Person Name
Nicolaas Lumen
Contact Person Email
Nicolaas.Lumen@UZGENT.be
Site Name
Institut Jules Bordet
Department Name
Medical Oncology
Contact Person Name
Nieves Martinez-Chanzá
Site Name
Algemeen Ziekenhuis Groeninge
Department Name
Urologie
Contact Person Name
Karl Lesage
Contact Person Email
karl.lesage@azgroeninge.be

Bulgaria

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
05-03-2026
Processing Time Days
644
Number Of Sites
4
Number Of Participants
21

Sites

Site Name
University Specialized Hospital For Active Treatment In Oncology EAD
Department Name
Clinic of medical oncology
Contact Person Name
Assia Konsoulova
Contact Person Email
Dr.konsoulova@gmail.com
Site Name
UMHAT Sofiamed OOD
Department Name
Medical oncology
Contact Person Name
Velko Minchev
Contact Person Email
v_minchev@abv.bg
Site Name
Complex Oncological Center Plovdiv EOOD
Department Name
Department of medical oncology and oncology gastroenterology diseases
Contact Person Name
Antoaneta Tomova
Contact Person Email
dr.tomova@gmail.com
Site Name
Multiprofessional Hospital For Active Treatment Park Hospital Ltd.
Department Name
Department of medical oncology
Contact Person Name
Vladimir Kanarev
Contact Person Email
kanarevi@abv.bg

Slovakia

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
641
Number Of Sites
6
Number Of Participants
23

Sites

Site Name
Uroexam spol. s r.o.
Department Name
Outpatient Care of Urology
Contact Person Name
Marek Brezovský
Contact Person Email
uroexam@gmail.com
Site Name
Milab s.r.o.
Department Name
Outpatient Care of Urology
Contact Person Name
Ivan Minčík
Contact Person Email
mincik@fnsp.presov.sk
Site Name
Urocentrum Sala s.r.o.
Department Name
Outpatient Care of Urology
Contact Person Name
Richard Polák
Contact Person Email
risiak333@gmail.com
Site Name
URO clinic s.r.o.
Contact Person Name
Boris Kollárik
Contact Person Email
bkollarik@gmail.com
Site Name
Privatna Urologicka Ambulancia s.r.o.
Department Name
Outpatient Care of Urology
Contact Person Name
Roman Sokol
Contact Person Email
roman.sokol@urology.sk
Site Name
Cuimed s.r.o.
Department Name
Outpatient Care of Urology
Contact Person Name
Frederico Goncalves
Contact Person Email
cuimed1@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
07-03-2026
Processing Time Days
646
Number Of Sites
9
Number Of Participants
38

Sites

Site Name
Clinical Research Center Sp. z o.o. Medic-R sp.k.
Contact Person Name
Ilona Bar-Letkiewicz
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Onkologii i Radioterapii
Contact Person Name
Renata Zaucha
Contact Person Email
rzaucha@gumed.edu.pl
Site Name
Szpital Kliniczny Ministerstwa Spraw Wewnetrznych I Administracji Z Warminsko-Mazurskim Centrum Onkologii W Olsztynie
Department Name
Oddzial Kliniczny Onkologii i Immunoonkologii z Osrodkiem Dziennym Terapii Onkologicznej
Contact Person Name
Karolina Zukowska
Contact Person Email
karolina.gornowicz@wp.pl
Site Name
Szpital Grochowski Im.Dr Med. Rafała Masztaka Sp. z o.o.
Department Name
Oddzial Chemioterapii
Contact Person Name
Iwona Skoneczna
Contact Person Email
iskoneczna@grochowski.waw.pl
Site Name
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
Department Name
Oddzial Dzienny Chemioterapii
Contact Person Name
Mariusz Kwiatkowski
Contact Person Email
mariusz.kwiatkowski@swk.med
Site Name
Nasz Lekarz Przychodnie Medyczne Sp. z o.o.
Contact Person Name
Przemyslaw Adamczyk
Contact Person Email
przemekad@poczta.onet.pl
Site Name
Centrum Medyczne Medyk Sp. z o.o.
Contact Person Name
Kamil Kuc
Contact Person Email
kkuc@wszp.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium Chemioterapii i Oddzial Kliniczny Radioterapii
Contact Person Name
Bogdan Zurawski
Contact Person Email
zurawskib@co.bydgoszcz.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworow Ukladu Moczowego
Contact Person Name
Pawel Wiechno
Contact Person Email
wiechno@gmail.com

Netherlands

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
16-03-2026
Processing Time Days
655
Number Of Sites
5
Number Of Participants
27

Sites

Site Name
Elisabeth-Tweesteden Ziekenhuis
Department Name
Interne Geneeskunde
Contact Person Name
Robbert van Alphen
Contact Person Email
r.vanalphen@etz.nl
Site Name
Bravis Ziekenhuis
Department Name
Interne/Oncologie centrum
Contact Person Name
Steve Boudewijns
Contact Person Email
s.boudewijns@bravis.nl
Site Name
Tergooiziekenhuizen
Department Name
Interne Geneeskunde
Contact Person Name
Pieter van den Berg
Contact Person Email
PvandenBerg@tergooi.nl
Site Name
St. Antonius Ziekenhuis
Department Name
Interne Geneeskunde
Contact Person Name
Jarmo Hunting
Site Name
Haga Hospital
Department Name
Interne/Oncologie
Contact Person Name
Daniel Houtsma
Contact Person Email
d.houtsma@hagaziekenhuis.nl

Germany

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
04-03-2026
Processing Time Days
643
Number Of Sites
9
Number Of Participants
22

Sites

Site Name
Charite Research Organisation GmbH
Department Name
Uro-Onkologisches Studiendepartment
Contact Person Name
Maria de Santis
Contact Person Email
maria.de-santis@charite.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Klinik für Urologie und Kinderurologie
Contact Person Name
Martin Boegemann
Contact Person Email
uroonkologie@ukmuenster.de
Site Name
Klinikum Nuernberg
Department Name
Onkologie/ Haematologie
Contact Person Name
Marinela Augustin
Site Name
Urologie Neandertal
Department Name
Urologie
Contact Person Name
Philipp Spiegelhalder
Site Name
Urologische Gemeinschaftspraxis
Department Name
Urologie
Contact Person Name
Miguel Garcia Schuermann
Contact Person Email
dr.garcia@urologie-wesel.de
Site Name
Marien Hospital Herne Universitatsklinikum Der Ruhr-Universitat Bochum
Department Name
Klinik für Urologie
Contact Person Name
Florian Roghmann
Site Name
Studienpraxis Urologie Susan Feyerabend MD Tilman Todenhoefer MD PhD GbR
Department Name
Urologie
Contact Person Name
Susan Feyerabend
Contact Person Email
praxis@studienurologie.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Studienbetreuung der Martini Klinik am UKE GmbH
Contact Person Name
Thomas Steuber
Contact Person Email
steuber@uke.de
Site Name
Urologicum Duisburg
Department Name
Urologie
Contact Person Name
Eva Hellmis
Contact Person Email
praxis@urologicum-duisburg.de

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Third parties

  • {"country":"Sweden","full_name":"AstraZeneca AB","duties_or_roles":"Monetary support","organisation_type":"Pharmaceutical company"}
  • {"country":"","full_name":"Astrazeneca K.K.","duties_or_roles":"Monetary support","organisation_type":""}

Investigational products

Investigational Product Name
Capivasertib
Active Substance
CAPIVASERTIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus: 1
Investigational Product Name
ABIRATERONE ACETATE
Active Substance
ABIRATERONE ACETATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus: 2
Investigational Product Name
Placebo for capivasertib film-coated tablet for oral use
Modality
Other
Combination Treatment
Yes

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