A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer

Official title

A Phase II, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy and Safety of the Combination of Inavolisib Plus Enzalutamide Versus Physician's Choice of ARPI or Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer

Overview

This study will evaluate the efficacy and safety of the combination of inavolisib plus enzalutamide compared with physician's choice of alternative androgen receptor pathway inhibitor (ARPi) or docetaxel in biomarker-selected participants with metastatic castrate-resistant prostate cancer (mCRPC) who have received one prior second-generation ARPi.

Interventions

• Drug Inavolisib
  Inavolisib will be administered orally as per the schedule specified in the protocol.
• Drug Enzalutamide
  Enzalutamide will be administered orally as per the schedule specified in the protocol.
• Drug Abiraterone
  Abiraterone will be administered orally as per the schedule specified in the protocol.
• Drug Docetaxel
  Docetaxel will be administered intravenously as per the schedule specified in the protocol.

Primary outcome measures

• Radiographic Progression-free Survival (rPFS) [Time frame: Up to approximately 5 years]

Secondary outcome measures (7)

• Percentage of Participants with Confirmed Composite Response Rate (RR) [Time frame: Up to approximately 5 years]
• Percentage of Participants with Confirmed Prostate-Specific Antigen 90 (PSA90) [Time frame: Up to approximately 5 years]
• Percentage of Participants with Confirmed Prostate-Specific Antigen 50 (PSA50) [Time frame: Up to approximately 5 years]
• Objective Response Rate (ORR) [Time frame: Up to approximately 5 years]
• Duration of Response (DOR) [Time frame: Up to approximately 5 years]
• Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Percentage of Participants With Adverse Events (AEs) [Time frame: Up to approximately 5 years]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small-cell or neuroendocrine features
• Progressive metastatic CRPC, defined as any of the following: PSA progression, defined by a minimum of two rising PSA values from three consecutive assessments with an interval of at least 7 days between assessments and with a minimal starting value of PSA >=1 ng/mL; The most recent qualifying PSA value must be determined within 14 days of enrollment; Soft tissue disease progression, defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); Bone disease progression, defined by PCWG3 criteria, with two or more new metastatic bone lesions on a whole-body radionuclide bone scan
• Treatment with at least one, but no more than one, prior second-generation ARPi (abiraterone, apalutamide, enzalutamide, darolutamide) for hormone- sensitive prostate cancer (HSPC) or CRPC
• Availability of a tumor tissue specimen that is suitable (e.g., adequate quality and quantity) for use in determining biomarker status
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Fasting glucose <100 mg/dL and HbA1c < 5.7%

Exclusion criteria

• Presence of liver metastasis
• Prior treatment with any phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or with any agent with a mechanism of action of inhibiting the PI3K/AKT/mTOR pathway
• Type 1 or Type 2 diabetes mellitus
• Prior treatment for mCRPC with cytotoxic chemotherapy or novel hormonal treatments (e.g., androgen receptor degraders, CYP11 inhibitors), with the following treatments permitted: Prior docetaxel in mHSPC, providing no evidence of disease progression occurred during treatment or within 6 months of treatment completion; Prior docetaxel in the adjuvant or neoadjuvant setting providing no evidence of disease progression occurred during treatment or within 12 months of treatment completion; Prior treatment with sipuleucel-T, with the last dose administered >28 days prior to start of treatment; Prior PARPi therapy, as per local prescribing information, with the last dose administered >14 days prior to start of treatment; One prior RLT or radiotherapeutic agent (e.g., PSMA-targeted RLT, Radium 223) with the last dose administered >8 weeks prior to start of treatment
• Other concurrent anti-cancer therapy except for androgen deprivation therapy
• Treatment with strong CYP2C8 inhibitors, strong or moderate CYP2C8 inducers, or strong CYP3A4 inducers within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment
• Transfusion of any blood product for the sole purpose of making a potential participant eligible for study inclusion or within 28 days of enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• VA West Los Angeles Medical Center - (CRS) - NAVREF - PPDS — Los Angeles
• UCSF — San Francisco
• Holden Comprehensive Cancer Center — Iowa City
• Montefiore Einstein Cancer Center — The Bronx
• Lifespan Cancer Institute — Providence
• Carolina Urologic Research Center — Myrtle Beach

Brazil · 5 centers

• Irmandade Da Santa Casa de Misericordia de Porto Alegre — Porto Alegre
• CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia — Santo André
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS — São José do Rio Preto
• Instituto Nacional de Cancer - INCa — Rio de Janeiro
• Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESP — São Paulo

South Korea · 5 centers

• Seoul National University Bundang Hospital — Seongnam-si
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center. — Seoul
• Samsung Medical Center — Seoul

Turkey (Türkiye) · 5 centers

• Ankara Universitesi Tip Fakultesi Hastaneleri - Cebeci Hastanesi — Ankara
• VM Medical Park Samsun Hastanesi — Atakum
• Koc Universitesi Hastanesi — Istanbul
• Izmir Medical Point Hospital — Izmir
• Medical Park Seyhan Hospital — Seyhan

Australia · 4 centers

• Royal North Shore Hospital-Pacific Hwy — St Leonards
• Sunshine Coast University Hospital — Birtinya
• Royal Brisbane & Womens Hospital — Herston
• Box Hill Hospital — Box Hill

France · 4 centers

• EDOG - Institut Bergonie - PPDS — Bordeaux
• Gustave Roussy — Villejuif
• Centre Léon Bérard — Lyon
• Institut Paoli Calmettes — Marseille

Spain · 4 centers

• Hospital Universitario Cruces — Barakaldo
• C.H. Regional Reina Sofia - PPDS — Córdoba
• Hospital Universitario 12 de Octubre — Madrid
• Fundacion Instituto Valenciano de Oncologia (IVO) — Valencia

Canada · 3 centers

• Princess Margaret Cancer Centre — Toronto
• Centre de recherche du Centre Hospitalier de l'Universite de Montreal — Montreal
• Jewish General Hospital — Montreal

Germany · 3 centers

• Universitätsklinikum Freiburg — Freiburg im Breisgau
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Studienpraxis Urologie — Nürtingen

Italy · 3 centers

• Istituti Fisioterapici Ospitalieri — Rome
• Ospedale San Raffaele S.r.l. - PPDS — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan

Mexico · 3 centers

• Hospital MAC León — León
• Productos y Servicios Oncologicos Acacias SA de CV — Benito Juárez
• Health Pharma Professional Research S.A de C.V. — Mexico City

United Kingdom · 2 centers

• The Royal Marsden in Sutton, Surrey - Downs Rd — Sutton
• Velindre Cancer Centre — Cardiff

Identifiers

NCT: NCT07287150 · CO45813 · 2025-521327-67-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗