A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1) (Himalayas-1)
20. července 2026 aktualizováno: ORIC Pharmaceuticals
A Phase 3, Randomized, Open-Label Study of Rinzimetostat (ORIC-944) in Combination With Darolutamide Compared With ARPI or Docetaxel in Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Abiraterone Acetate (Himalayas-1)
Himalayas-1 is a randomized, open-label, global, multicenter phase 3 study evaluating whether the combination of rinzimetostat with darolutamide is more effective compared to physician's choice of control; ARPI (darolutamide or enzalutamide) or docetaxel for treating patients with metastatic castration resistant prostate cancer (mCRPC) who were previously treated with abiraterone acetate.
The primary objective of this study is to demonstrate superiority in radiographic progression free survival (rPFS) of the investigational arm of rinzimetostat + darolutamide combination versus physician's choice of control: ARPI (darolutamide or enzalutamide) or docetaxel.
Přehled studie
Postavení
Nábor
Intervence / Léčba
Typ studie
Intervenční
Zápis (Odhadovaný)
600
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: ORIC Clinical Call Center
- E-mail: clinical@oricpharma.com
Studijní místa
-
-
North Carolina
-
Charlotte, North Carolina, Spojené státy, 29464
- Nábor
- Urology Specialists of the Carolinas - University Place
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Vrchní vyšetřovatel:
- Jeremy Hubbard, MD
-
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Utah
-
Murray, Utah, Spojené státy, 84107
- Nábor
- Summit Urology
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Vrchní vyšetřovatel:
- Stewart Landau, MD
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Popis
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
- Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required
- Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
Exclusion Criteria:
Prior treatment for prostate cancer at any stage with cytotoxic chemotherapy, radioligand therapy (ie, 177Lu -PSMA-617, radium-223), ARPIs including apalutamide, darolutamide, and enzalutamide, PARP monotherapy or other systemic anticancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene or cell therapy, angiogenesis inhibitors, CDK4/6 inhibitors, PRC2 inhibitors) with the following exceptions:
- Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
- Docetaxel treatment is allowed for mCSPC, as long as no signs of failure or disease progression occurred during treatment or within 3 months of treatment completion
- Any other anticancer therapy (drug or vaccine which does not meet exclusion criterion 1 above) within 28 days or 5 half-lives (whichever is longer) prior to randomization
- Known or suspected brain metastasis or active leptomeningeal disease
- Clinically significant cardiovascular disease defined as:
- Any medical (including active or clinically significant bacterial, fungal, or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the patient inappropriate for the study
- Active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery are excluded
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Aktivní komparátor: Investigational Arm
Rinzimetostat + darolutamide
|
400 mg once daily (QD)
Ostatní jména:
600 mg twice daily (BID)
Ostatní jména:
|
|
Aktivní komparátor: Physician's Choice
Control Arm
|
600 mg twice daily (BID)
Ostatní jména:
160 mg once daily (QD)
Ostatní jména:
75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Časové okno: Randomization up to ~2 years
|
Radiographic Progression Free Survival is defined as the time from the date of randomization to first evidence of radiographic progression as assessed in soft tissue by RECIST 1.1 or in bone per PCWG3 guideline by BICR, or death, whichever occurs first
|
Randomization up to ~2 years
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Survival (OS)
Časové okno: 5 years
|
OS is defined as time from date of randomization to date of death due to any cause
|
5 years
|
|
Objective response rate (ORR)
Časové okno: Randomization up to ~2 years
|
ORR is defined as proportion of patients with measurable soft tissue disease at baseline who have a confirmed objective response of complete response (CR) or partial response (PR)
|
Randomization up to ~2 years
|
|
Duration of Response (DoR)
Časové okno: Randomization up to ~2 years
|
DOR is defined as time of first response to first documentation of radiographic progression or death, whichever occurs first
|
Randomization up to ~2 years
|
|
Prostate Specific Antigen (PSA) response
Časové okno: Randomization up to ~2 years
|
Defined as the proportion of patients with a confirmed ≥50% and ≥90% decline in PSA from baseline as per the PCWG3 criteria, along with the maximum decline in PSA occurring at any point on study
|
Randomization up to ~2 years
|
|
Time to PSA progression
Časové okno: Randomization up to ~2 years
|
Measured from the start of treatment until criteria for PSA progression are met as per PCWG3
|
Randomization up to ~2 years
|
|
Time to initiation of antineoplastic therapy
Časové okno: Randomization up to ~4 years
|
Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)
|
Randomization up to ~4 years
|
|
Time to first symptomatic skeletal event
Časové okno: Randomization up to ~4 years
|
Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first) Compare patient reported outcomes (PROs) between the investigational treatment and control arms
|
Randomization up to ~4 years
|
|
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)
Časové okno: Randomization up to ~4 years
|
Analysis of Brief Pain Inventory-Short Form (BPI-SF) will be based on the pain severity score (mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (the mean of items 9A-9G), and the single BPI-SF Item 3 which asks the patient to rate pain at its worst in the last 24 hours
|
Randomization up to ~4 years
|
|
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Časové okno: Randomization up to ~4 years
|
Change from baseline in HRQoL (FACT-P total score) will be presented.
The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire.
Each item is rated on a 0 to 4 Likert-type scale and then combined to produce the FACT-P total score (0-156), with higher scores representing better health-related quality of life
|
Randomization up to ~4 years
|
|
Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Časové okno: Randomization up to ~4 years
|
Change from baseline in social/family well-being score will be presented.
The social/family well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28.
Each item is rated on a 0 to 4 Likert-type scale
|
Randomization up to ~4 years
|
|
Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Časové okno: Randomization up to ~4 years
|
Change from baseline in functioning well-being score will be presented.
The functioning well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28.
Each item is rated on a 0 to 4 Likert-type scale
|
Randomization up to ~4 years
|
|
Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Časové okno: Randomization up to ~4 years
|
Change from baseline in physical well-being score will be presented.
The physical well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28.
Each item is rated on a 0 to 4 Likert-type scale
|
Randomization up to ~4 years
|
|
Change from baseline in symptoms per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Časové okno: Randomization up to ~4 years
|
Change from baseline prostate cancer symptoms (PCS) score will be presented.
The PCS score will be calculated based on 12 items in the FACT-P questionnaire; score range 0-48.
Each item is rated on a 0 to 4 Likert-type scale
|
Randomization up to ~4 years
|
|
Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)
Časové okno: Randomization up to ~4 years
|
Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension.
The questionnaire also includes a visual analog scale to self-rate general health state on a scale from "the worst health you can imagine" to "the best health you can imagine."
|
Randomization up to ~4 years
|
|
Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)
Časové okno: Randomization up to ~2 years
|
Each selected PRO-CTCAE items will be assessed related to one or more attributes that include counts for the frequency, severity, and/or interference with usual or daily activities
|
Randomization up to ~2 years
|
|
Overall side effect burden as measured by the FACT- GP5
Časové okno: Randomization up to ~2 years
|
The FACT-GP5 question assesses overall side effect burden with the following response options "I am bothered by side effects of treatment," is rated on a 5-point scale ranging from "not at all" (0) to "very much" (4) and counts will be presented
|
Randomization up to ~2 years
|
|
Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours"
Časové okno: Randomization up to ~4 years
|
Defined as the time from randomization to onset of pain progression, which is defined as > 2-point increase from baseline in the score from the BPI-SF Question 3 that is confirmed at the next consecutive assessment > 4 weeks apart or an initial deterioration followed by death before the next assessment
|
Randomization up to ~4 years
|
|
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P
Časové okno: Randomization up to ~4 years
|
Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as >10 point decrease from baseline and no subsequent observations with a <10 point decrease from baseline FACT-P total score
|
Randomization up to ~4 years
|
|
Time to definitive deterioration in patient-reported physical well-being per FACT-P
Časové okno: Randomization up to ~4 years
|
Time to definitive deterioration in physical well-being (PWB) per FACT-P is defined as the time from randomization to onset of definitive deterioration in physical well-being, which is defined as ≥3-point
|
Randomization up to ~4 years
|
|
Incidence of Adverse Events (AEs)
Časové okno: Randomization up to ~2 years
|
Type, incidence, relationship to study treatments, severity, and seriousness of AEs [as graded by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v6.0] and other clinical assessments
|
Randomization up to ~2 years
|
|
Evaluate the pharmacokinetics (PK) of rinzimetostat in combination with darolutamide
Časové okno: Randomization up to ~1 year
|
Rinzimetostat characterized by predose and postdose plasma concentrations at selected time points
|
Randomization up to ~1 year
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
1. července 2026
Primární dokončení (Odhadovaný)
1. března 2028
Dokončení studie (Odhadovaný)
1. září 2030
Termíny zápisu do studia
První předloženo
18. června 2026
První předloženo, které splnilo kritéria kontroly kvality
20. července 2026
První zveřejněno (Aktuální)
23. července 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
23. července 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
20. července 2026
Naposledy ověřeno
1. července 2026
Více informací
Termíny související s touto studií
Klíčová slova
- bezpečnost
- rakovina prostaty
- otevřený
- účinnost
- enzalutamid
- abirateron
- recidivovala
- žáruvzdorný
- pokročilého karcinomu prostaty
- docetaxel
- odolný vůči hormonům
- abirateron acetát
- darolutamid
- metastatický kastračně rezistentní karcinom prostaty (mCRPC)
- hormone dependent malignancy
- androgen receptor (AR) signaling
- androgen pathway modulator-resistant (APMR)
- metastatic castration sensitive prostate cancer (mCSPC)
- androgen pathway modulator-naïve/sensitive (APMN/S)
- polycomb repressive complex 2 (PRC2)-controlled dysregulation
- embryonic ectoderm development (EED)
- enhancer of zeste homolog 2 (EZH2)
- ORIC-944
- rinzimetostat
- mevrometostat
Další relevantní podmínky MeSH
- Urogenitální onemocnění
- Onemocnění genitálií
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Patologické procesy
- Genitální novotvary, muži
- Urogenitální novotvary
- Novotvary podle místa
- Novotvary
- Onemocnění pohlavních orgánů, muž
- Onemocnění prostaty
- Mužská urogenitální onemocnění
- Neuromuskulární onemocnění
- Atributy nemoci
- Genetické choroby, vrozené
- Neurodegenerativní onemocnění
- Heredodegenerativní poruchy, nervový systém
- Genetická onemocnění, vázaná na X
- Nemoci míchy
- Nemoc motorických neuronů
- Svalová atrofie, Spinální
- Vrozené, dědičné a neonatální nemoci a abnormality
- Patologické stavy, příznaky a symptomy
- Novotvary prostaty
- Opakování
- Bulbo-spinální atrofie, X-Linked
- Organické chemikálie
- Uhlovodíky
- Cykloparafiny
- Uhlovodíky, alicyklické
- Uhlovodíky, cyklické
- Terpeny
- Taxoidy
- Cyclodecanes
- Diterpeny
- Docetaxel
- darolutamid
- Enzalutamid
Další identifikační čísla studie
- ORIC-944-05
- 2026-525340-15-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
NE
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ano
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
produkt vyrobený a vyvážený z USA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .