Clinical trial • Phase I/II • Oncology

OPEVESOSTAT TOSILATE for Metastatic castration-resistant prostate cancer

Phase I/II trial of OPEVESOSTAT TOSILATE for Metastatic castration-resistant prostate cancer. Randomised, adaptive. 184 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic castration-resistant prostate cancer
Trial Stage
Phase I/II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
08-04-2024
First CTIS Authorization Date
23-07-2024

Trial design

Randomised, adaptive Phase I/II trial across 29 sites in Poland, Italy, Germany and others.

Randomised
Yes
Adaptive
True, Safety lead-in (dose-escalation) to evaluate safety/tolerability and establish an RP2D; primary endpoints include DLTs to inform dose escalation decisions.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
184

Eligibility

Recruits 184 No vulnerable populations selected; trial enrolls adult male participants only. Informed consent is required from each participant; optional limited screening consent and other optional ICF modules are available. No assent/consent procedures for minors are indicated..

Vulnerable Population
No vulnerable populations selected; trial enrolls adult male participants only. Informed consent is required from each participant; optional limited screening consent and other optional ICF modules are available. No assent/consent procedures for minors are indicated.

Inclusion criteria

  • {"criterion_text":"- Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology."}
  • {"criterion_text":"- Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable."}
  • {"criterion_text":"- Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening."}
  • {"criterion_text":"- Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy."}
  • {"criterion_text":"- Current evidence of metastatic disease."}
  • {"criterion_text":"- Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment."}
  • {"criterion_text":"- Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks before randomization."}
  • {"criterion_text":"- Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline."}
  • {"criterion_text":"- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy."}
  • {"criterion_text":"- Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load."}

Exclusion criteria

  • {"criterion_text":"- History of pituitary dysfunction."}
  • {"criterion_text":"- Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention."}
  • {"criterion_text":"- Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization)."}
  • {"criterion_text":"- Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization."}
  • {"criterion_text":"- Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids."}
  • {"criterion_text":"- Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed."}
  • {"criterion_text":"- Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention."}
  • {"criterion_text":"- Known additional malignancy that is progressing or has required active treatment within the past 3 years."}
  • {"criterion_text":"- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis."}
  • {"criterion_text":"- Active autoimmune disease that has required systemic treatment in the past 2 years."}
  • {"criterion_text":"- Active infection requiring systemic therapy."}
  • {"criterion_text":"- Poorly controlled diabetes mellitus."}
  • {"criterion_text":"- Concurrent active HBV or HCV infections."}
  • {"criterion_text":"- Active or unstable cardio/cerebro-vascular disease, including thromboembolic events and history of stroke or transient ischemic attack within 6 months before the first dose of study intervention, history of myocardial infarction within 6 months before the first dose of study intervention, New York Heart Association Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina"}
  • {"criterion_text":"- History or family history of long corrected QT interval (QTc) syndrome."}
  • {"criterion_text":"- Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML."}
  • {"criterion_text":"- History or current condition of adrenal insufficiency."}
  • {"criterion_text":"- History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis."}
  • {"criterion_text":"- HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease."}
  • {"criterion_text":"- Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Number of participants who experience one or more dose-limiting toxicities (DLTs)","definition_or_measurement_approach":"Count of participants experiencing one or more DLTs (specific DLT definition/assessment period not provided in the available data)."}
  • {"endpoint_text":"- Number of participants who experience one or more adverse events (AEs)","definition_or_measurement_approach":"Count of participants with one or more AEs (specific AE grading/period not provided in the available data)."}
  • {"endpoint_text":"- Number of participants who discontinue study intervention due to an AE","definition_or_measurement_approach":"Count of participants discontinuing study intervention because of an AE (criteria for discontinuation not detailed in provided data)."}
  • {"endpoint_text":"- Prostate-specific antigen (PSA) response rate","definition_or_measurement_approach":"PSA response rate (definition/threshold for response not specified in the provided data)."}

Secondary endpoints

  • {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":"ORR assessed per PCWG Modified RECIST 1.1 as evaluated by blinded independent central review (BICR)."}
  • {"endpoint_text":"- Radiographic progression-free survival (rPFS)","definition_or_measurement_approach":"rPFS assessed per PCWG Modified RECIST 1.1 as evaluated by BICR."}
  • {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"OS defined as time from randomization (or specified baseline) to death from any cause (specific censoring rules not provided)."}
  • {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"DOR as assessed by BICR (specific criteria/time windows not provided)."}
  • {"endpoint_text":"- Time to first subsequent anticancer therapy (TFST)","definition_or_measurement_approach":"TFST defined as time to initiation of first subsequent anticancer therapy."}
  • {"endpoint_text":"- Time to pain progression (TTPP)","definition_or_measurement_approach":"TTPP defined as time to progression of pain (specific pain assessment instrument not provided)."}

Recruitment

Digital Remote Recruitment
True, social media adverts (Finland) and country-specific recruitment websites and online recruitment materials are included; eCOA/electronic patient questionnaires and online recruitment brochures are present in documentation.
Planned Sample Size
184
Recruitment Window Months
43
Consent Approach
Informed consent obtained from each participant (adult male). Country-specific main informed consent forms (ICF) and optional ICF modules are provided; optional limited screening consent is available. ICFs and recruitment materials are available in local languages as indicated (examples in documentation: PL, IT, DE, EN, FI, FR, ES). No assent procedures for minors are indicated.

Methods

  • K2_Recruitment Doc Social Media_0602_FIN_FI_for pub — social media recruitment (Finland) as documented
  • K2_Recruitment Doc Advertisement_0602_FIN_FI_for pub — advertisement materials (Finland) as documented
  • K2_Recruitment Doc Website_POL_PL_SM04_for pub — recruitment website/materials (Poland) as documented
  • K2_Recruitment Doc Patient Brochure_* — patient brochure materials (country-specific patient brochures available)
  • K1_Recruitment Arrangements and IC Procedure_* — recruitment arrangements and informed consent procedure documents provided for multiple countries (country-specific)

Geography

Total Number Of Sites
29
Total Number Of Participants
127

Poland

Earliest CTIS Part Ii Submission Date
16-07-2024
Latest Decision Or Authorization Date
08-09-2025
Processing Time Days
419
Number Of Sites
3
Number Of Participants
16

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz
Contact Person Name
Katarzyna Sosińska-Mielcarek
Contact Person Email
obkwf@uck.gda.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Oddział Badań Wczesnych Faz
Contact Person Name
Iwona Ługowska
Contact Person Email
obwf@nio.gov.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium Chemioterapii
Contact Person Name
Bogdan Żurawski

Italy

Earliest CTIS Part Ii Submission Date
07-06-2024
Latest Decision Or Authorization Date
08-09-2025
Processing Time Days
458
Number Of Sites
4
Number Of Participants
22

Sites

Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Contact Person Name
Andrea Zivi
Contact Person Email
andrea.zivi@aovr.veneto.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Struttura Complessa Oncologia MEdica 1
Contact Person Name
Elena Verzoni
Site Name
Humanitas Research Hospital
Department Name
U.O. di Oncologia medica ed Ematologia
Contact Person Name
Paolo Andrea Zucali
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Medical Oncology
Contact Person Name
Giampaolo Tortora

Germany

Earliest CTIS Part Ii Submission Date
13-06-2024
Latest Decision Or Authorization Date
15-09-2025
Processing Time Days
459
Number Of Sites
5
Number Of Participants
15

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Department for Urology
Contact Person Name
Maria de Santis
Contact Person Email
uro-onkologie@charite.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Department for Urology
Contact Person Name
Steffen Rausch
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Department of Internal Medicine II Oncological Clinical Trials Center
Contact Person Name
Gunhild von Amsberg
Contact Person Email
g.von-amsberg@uke.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Clinic for medical oncology
Contact Person Name
Stefanie Zschäbitz
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Urologische Klinik und Poliklinik
Contact Person Name
Margitta Retz
Contact Person Email
Margitta.Retz@tum.de

Ireland

Earliest CTIS Part Ii Submission Date
10-07-2024
Latest Decision Or Authorization Date
04-09-2025
Processing Time Days
421
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Cork University Hospital
Department Name
Oncology
Contact Person Name
Richard Bambury
Contact Person Email
richard.bambury@merck.com
Site Name
St Vincent's University Hospital
Department Name
Oncology
Contact Person Name
Raymond McDermott
Contact Person Email
Ray.mcdermott@ccrt.ie
Site Name
Tallaght University Hospital
Department Name
Oncology
Contact Person Name
Raymond McDermott
Contact Person Email
Ray.mcdermott@tuh.ie

Finland

Earliest CTIS Part Ii Submission Date
12-07-2024
Latest Decision Or Authorization Date
05-09-2025
Processing Time Days
420
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
HUS-Yhtymae
Department Name
HUS Cancer Center
Contact Person Name
Heikki Junkkari
Contact Person Email
heikki.junkkari@hus.fi
Site Name
Vaasa Central Hospital
Department Name
Department of Clinical Ongology
Contact Person Name
Ravichandra Ravi
Contact Person Email
ravichandra.ravi@ovph.fi
Site Name
Docrates Oy
Department Name
Docrates Cancer Center
Contact Person Name
Jorma Sormunen
Contact Person Email
jorma.sormunen@docrates.fi

Denmark

Earliest CTIS Part Ii Submission Date
16-07-2024
Latest Decision Or Authorization Date
17-09-2025
Processing Time Days
428
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Herlev Hospital
Department Name
Department of Oncology
Contact Person Name
Per Kongsted
Contact Person Email
per.kongsted@regionh.dk
Site Name
Aalborg University Hospital
Department Name
Department of Oncology
Contact Person Name
Mette Moe
Contact Person Email
mmk@rn.dk

Spain

Earliest CTIS Part Ii Submission Date
12-07-2024
Latest Decision Or Authorization Date
25-09-2025
Processing Time Days
440
Number Of Sites
5
Number Of Participants
20

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Contact Person Name
David Marmolejo Castañeda
Contact Person Email
davidmarmolejo@vhio.net
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Medical Oncology
Contact Person Name
Teresa Alonso Gordoa
Contact Person Email
talonsogordoa@gmail.com
Site Name
Hospital Clinico San Carlos
Department Name
Medical Oncology
Contact Person Name
Javier Puente Vazquez
Contact Person Email
javierpuente.hcsc@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Medical Oncology
Contact Person Name
Jose Angel Arranz Arija
Contact Person Email
jarranza.oncomed@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Medical Oncology
Contact Person Name
Josep Piulats
Contact Person Email
jmpiulats@iconcologia.net

France

Earliest CTIS Part Ii Submission Date
16-07-2024
Latest Decision Or Authorization Date
27-01-2026
Processing Time Days
560
Number Of Sites
4
Number Of Participants
28

Sites

Site Name
Institut Bergonie
Department Name
Oncology
Contact Person Name
Guilhem Roubaud
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Medical Oncology
Contact Person Name
Philippe Barthélémy
Contact Person Email
p.barthelemy@icans.eu
Site Name
Institut Gustave Roussy
Department Name
Medical Oncology
Contact Person Name
Natacha Naoun
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Medical Oncology
Contact Person Name
Stéphane Oudard
Contact Person Email
stephane.oudard@aphp.fr

Sponsor

Primary sponsor

Full Name
Merck Sharp & Dohme LLC
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Parexel International Corp.
Responsibilities
Medical information (Physician Consulting) &EUB Call center and medical escalation service
Name
Almac Clinical Services LLC
Name
Bioclinica Inc.
Responsibilities
Central Imaging
Name
Eresearchtechnology Inc.
Name
Ardena Bioanalysis B.V.

Third parties

  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Medical information (Physician Consulting) &EUB Call center and medical escalation service","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central Imaging","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Opevesostat
Active Substance
OPEVESOSTAT TOSILATE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Investigational Product Name
DOCETAXEL
Active Substance
DOCETAXEL
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Investigational Product Name
CABAZITAXEL
Active Substance
CABAZITAXEL 2-PROPANOL SOLVATE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Investigational Product Name
Olaparib
Active Substance
OLAPARIB
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Combination Treatment
Yes

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