Montag, 23. Dezember 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE

A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)

Rekrutierend

NCT-Nummer:
NCT06136650

Studienbeginn:
Dezember 2023

Letztes Update:
08.08.2024

Wirkstoff:
Opevesostat, Dexamethasone, Fludrocortisone acetate, Hydrocortisone, abiraterone acetate, Prednisone acetate, Enzalutamide

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
Orion Corporation, Orion Pharma

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 201)

klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Sit
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 498941402522» Ansprechpartner anzeigen
Universitätsmedizin Göttingen - Georg-August-Universität-Klinik für Urologie ( Site 0527)
37075 Göttingen
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 495513968142» Ansprechpartner anzeigen
Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0528)
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49 351 458 4425» Ansprechpartner anzeigen
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)
92868 Orange
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 502-472-3237» Ansprechpartner anzeigen
Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0074)
60126 Elmhurst
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 630-527-3788» Ansprechpartner anzeigen
HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0072)
55426 Saint Louis Park
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 952-993-1290» Ansprechpartner anzeigen
HealthPartners Cancer Research Center-HealthPartners Cancer Center at Regions Hospital ( Site 0092)
55101 Saint Paul
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 952-993-1290» Ansprechpartner anzeigen
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
4029 Brisbane
AustraliaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 61402240196» Ansprechpartner anzeigen
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0210)
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 61385598339» Ansprechpartner anzeigen
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S
210000 NanJing
ChinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 8613605171690» Ansprechpartner anzeigen
The First Affiliated Hospital of Xi'an Jiaotong University-Oncology department ( Site 1618)
710061 Xi'an
ChinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 8615991752560» Ansprechpartner anzeigen
Renji Hospital Shanghai Jiao Tong University School of Medicine-Oncology Department ( Site 1624)
200127 Shanghai
ChinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 8613801931604» Ansprechpartner anzeigen
Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0379)
10903 Santa Ana
Costa RicaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 88308999» Ansprechpartner anzeigen
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0461)
33076 Bordeaux
FranceRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 33556333333» Ansprechpartner anzeigen
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne ( Site 0454)
63011 Clermont-Ferrand
FranceRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 33473278131» Ansprechpartner anzeigen
ATTIKON GENERAL UNIVERSITY HOSPITAL-2nd Dep. of Int. Medicine. Research Unit & Diabetes Center ( Sit
124 62 Chaidari
GreeceRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +306944861060» Ansprechpartner anzeigen
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás C
3526 Miskolc
HungaryRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 36204108060» Ansprechpartner anzeigen
Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 0631)
1122 Budapest
HungaryRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 36122486001171» Ansprechpartner anzeigen
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 14
47014 Meldola
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +390543739100» Ansprechpartner anzeigen
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1452)
20133 Milan
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 00390223903033» Ansprechpartner anzeigen
Hospital of the University of Occupational and Environmental Health, Japan ( Site 0746)
807-8556 Kitakyushu
JapanRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +81936031611» Ansprechpartner anzeigen
Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospi-Centro De Investigaçao Clínica ( Site 1
1649-035 Lisbon
PortugalRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 910333113» Ansprechpartner anzeigen
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1378)
34722 Istanbul
TurkeyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 00905063509061» Ansprechpartner anzeigen
Guy's & St Thomas' NHS Foundation Trust-Oncology & Haematology Clinical Trials ( Site 1435)
SE1 9RT London
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 004402071883761» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to assess the efficacy and safety of opevesostat plus

hormone replacement therapy (HRT) compared to alternative abiraterone acetate or

enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC)

previously treated with one next-generation hormonal agent (NHA). The primary study

hypotheses are that opevesostat is superior to alternative abiraterone acetate or

enzalutamide with respect to radiographic progression free survival (rPFS) per Prostate

Cancer Working Group (PCWG) Modified Response Evaluation Criteria in Solid Tumors (RECIST

1.1) as assessed by Blinded Independent Central Review (BICR) and overall survival (OS),

in androgen receptor ligand binding domain (AR LBD) mutation positive and negative

participants.

Ein-/Ausschlusskriterien

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

- Have histologically or cytologically confirmed adenocarcinoma of the prostate

without small cell histology

- Has current evidence of metastatic disease documented by either bone lesions on bone

scan and/or soft tissue disease shown by computed tomography scan (CT)/magnetic

resonance imaging (MRI)

- Has prostate cancer progression while receiving androgen deprivation therapy (ADT)

(or post bilateral orchiectomy) within 6 months before screening

- Has disease that progressed during or after treatment with one next-generation

hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) metastatic hormone

sensitive prostate cancer (mHSPC) or non metastatic hormone sensitive prostate

cancer (nmHSPC), for at least 8 weeks (at least 14 weeks for participants with bone

progression) Note: Participants may have received abiraterone acetate and docetaxel

or darolutamide and docetaxel for HSPC. However, participants must have received no

more than six cycles of docetaxel and had no radiographic disease progression while

receiving docetaxel

- Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed

within 7 days before randomization

- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)

- Has had prior treatment with Poly polymerase inhibitors (PARPi) or were deemed

ineligible to receive treatment by the investigator or have refused PARPi treatment

- Has adequate organ function

- Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue

not previously irradiated. Samples from tumors progressing at a prior site of

radiation are allowed

- 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 before randomization

- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV

viral load is undetectable at Screening

- Participants who have adverse event (AEs) due to previous anticancer therapies must

have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who

are adequately treated with hormone replacement therapy (HRT) or participants who

have ≤Grade 2 neuropathy are eligible

- Human immunodeficiency virus (HIV)-infected participants must have well controlled

HIV on antiretroviral therapy (ART)

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

- Has presence of gastrointestinal condition

- Is unable to swallow capsules/tablets

- Has history of pituitary dysfunction

- Has poorly controlled diabetes mellitus

- Has a history of active or unstable cardio/cerebro-vascular disease, including

thromboembolic events

- Has clinically significant abnormal serum potassium or sodium level

- Has any of the following at screening visit: Hypotension: systolic blood pressure

(BP) <110 mmHg, or Uncontrolled hypertension: systolic BP >160mmHg or diastolic

blood BP >90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive

therapy

- History or family history of long QTc syndrome

- Has a history of seizure(s) within 6 months prior to signing the informed consent

(IC) or has any condition that may predispose to seizure within 12 months prior to

the date of enrollment

- Has a history of clinically significant ventricular arrhythmias or Mobitz II second

degree or third-degree heart block without a permanent pacemaker in place

- Has received a taxane-based chemotherapy and or NHA for metastatic

castration-resistant prostate cancer (mCRPC)

- Has not adequately recovered from major surgery or have ongoing surgical

complications

- Has received prior treatment with radium for prostate cancer

- Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic

drugs for seizures

- Participants on an unstable dose of thyroid hormone therapy within 6 months before

the start of the study intervention

- Receives prior radiotherapy within 2 weeks before the first dose of study

intervention, or radiation-related toxicities, requiring corticosteroids

- Receives prior systemic anticancer therapy including investigational agents within 4

weeks before the first dose of study intervention

- Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein

(P-gp) inhibitors within 2 weeks before the first dose of study intervention

- Has received prior targeted small molecule therapy or NHA treatment within 4 weeks

before the first dose of study intervention

- Received a live or live-attenuated vaccine within 30 days before the first dose of

study intervention

- Has received an investigational agent or has used an investigational device within 4

weeks prior to study intervention administration

- Has known hypersensitivity to the components or excipients in abiraterone acetate,

prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or

opevesostat.

- Has a "superscan" bone scan defined as an intense symmetric activity in the bones

and diminished renal parenchymal activity on baseline bone scan such that the

presence of additional metastases in the future could not be evaluated

- Has known additional malignancy that is progressing or has required active treatment

within the past 3 years

- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in

dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior the first dose of study medication

- Has known active central nervous system (CNS) metastases and/or carcinomatous

meningitis. Participants with previously treated brain metastases may participate

provided they are radiologically stable, (ie, without evidence of progression) for

at least 4 weeks as confirmed by repeat imaging performed during study screening,

are clinically stable and have not required steroid treatment for at least 14 days

prior to the first dose of study intervention

- Has active autoimmune disease that has required systemic treatment in the past 2

years. Replacement therapy is allowed

- Active infection requiring systemic therapy

- Has concurrent active Hepatitis B virus and Hepatitis C virus infection

Studien-Rationale

Primary outcome:

1. Radiographic Progression-free Survival (rPFS) (Time Frame - Up to approximately 82 months):
rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.

2. Overall Survival (OS) (Time Frame - Up to approximately 82 months):
OS is defined as the time from randomization to death due to any cause.

Secondary outcome:

1. Time to Initiation of the First Subsequent Anticancer Therapy (TFST) (Time Frame - Up to approximately 82 months):
TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first.

2. Objective Response Rate (ORR) (Time Frame - Up to approximately 82 months):
ORR is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

3. Duration of Response (DOR) (Time Frame - Up to approximately 82 months):
For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death from any cause, whichever occurs first.

4. Time to Pain Progression (TTPP) (Time Frame - Up to approximately 82 months):
TTPP is defined as the time from randomization to pain progression. TTTP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm [AQA] Score).

5. Prostrate-specific Antigen (PSA) Response Rate (Time Frame - Up to approximately 82 months):
The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response.

6. Time to Prostate-specific Antigen (PSA) Progression (Time Frame - Up to approximately 82 months):
The time to PSA progression is the time from randomization to PSA progression. The PSA progression date is defined as the date of: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR 2) ≥25% increase and ≥2 ng/mL increase from baseline.

7. Time to first symptomatic skeletal-related event (TSSRE) (Time Frame - Up to approximately 82 months):
TSSRE is the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first.

8. Number of Participants Who Experience an Adverse Event (AE) (Time Frame - Up to approximately 82 months):
An AE is defined as any unfavorable and unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE will be reported.

9. Number of Participants Who Discontinue Study Treatment Due to an AE (Time Frame - Up to approximately 82 months):
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.

10. Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total Score (Time Frame - Baseline, and up to approximately 82 months):
The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The change from baseline in FACT-G total score will be reported.

11. Time to Deterioration (TTD) in FACT-G Total Score (Time Frame - Up to approximately 82 months):
The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. TTD in FACT-G total score will be reported.

12. Overall Improvement in FACT-G Total Score (Time Frame - Up to approximately 82 months):
The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The overall improvement in FACT-G total score will be reported.

Studien-Arme

  • Experimental: hormone replacement therapy (HRT)+ opevesostat
    Participants receive opevesostat 5 mg by oral tablets twice daily (BID) plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily (QD) continuously until disease progression. Hydrocortisone 100 mg (oral or intramuscular [IM]) will also be provided to participants for use as rescue medication.
  • Active Comparator: Alternative next generation hormonal agent (NHA)
    Participants receive Abiraterone 1000 mg QD by oral tablets plus Prednisone 5 mg BID by oral tablets or Enzalutamide 160 mg QD by oral tablets until disease progression.

Geprüfte Regime

  • Opevesostat (MK-5684):
    Administered orally
  • Dexamethasone:
    Administered orally
  • Fludrocortisone acetate:
    Administered orally
  • Hydrocortisone:
    Administered orally or IM as a rescue drug
  • Abiraterone acetate (Zytiga / Yonsa / ):
    Administered orally
  • Prednisone acetate:
    Administered orally
  • Enzalutamide (Xtandi):
    Administered orally

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.