Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

XB2001 i kombinasjon med ONIVYDE + 5-FU/LV (+folinsyre) ved avansert bukspyttkjertelkreft (1-BETTER)

9. juli 2026 oppdatert av: XBiotech, Inc.

En fase I/II randomisert, dobbeltblind, placebokontrollert studie (1-BEDRE) som undersøker XB2001 (Anti-IL-1⍺ ekte humant antistoff) i kombinasjon med ONIVYDE + 5-FU/LV (+folinsyre) i avansert Bukspyttkjertelkreft

Denne utprøvingen vil inkludere 2 porsjoner (fase 1 og fase 2).

Den første delen vil være en fase I, åpen doseeskaleringsstudie for å etablere maksimal tolerert dose (MTD) av XB2001 målt ved dosebegrensende toksisitet (DLT), i kombinasjon med ONIVYDE + LV + 5-FU kjemoterapiregime i pasienter med avansert kreft i bukspyttkjertelen og for å bestemme anbefalt dose for den påfølgende fase 2-studien.

Fase 2-delen vil bli implementert med den maksimale etablerte tolererte dosen (MTD) av XB2001. Målregistreringen i fase 2-delen er 60 pasienter som vil bli randomisert på 1:1-basis til XB2001 pluss ONIVYDE + LV + 5-FU (arm 1) eller placebo pluss ONIVYDE + LV + 5-FU (arm 2).

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Studietittel: En fase I/II randomisert, dobbeltblind, placebokontrollert studie (1-BETTER) som undersøker XB2001 (anti-IL-1⍺ True Human antistoff) i kombinasjon med ONIVYDE + 5-FU/LV (+folinsyre) ) ved avansert kreft i bukspyttkjertelen

Sponsor: XBiotech USA, Inc.

Studieleder: Benjamin Musher, M.D.

Prøvestørrelse: Omtrent 69 pasienter vil bli registrert i USA (minst 9 pasienter i den åpne fase 1-delen og 60 pasienter i den randomiserte fase 2-delen)

Omtrentlig varighet:

Denne utprøvingen vil omfatte 2 faser. Den første delen vil være en fase I, åpen, doseeskaleringsstudie som evaluerer sikkerheten, tolerabiliteten og etablerer den maksimale tolererte dosen (MTD) av XB2001 hos minst ni pasienter med metastatisk pankreasadenokarsinom som får ONIVYDE + Leucovorin l + d racemisk + 5-Fluorouracil kjemoterapibehandling. Varigheten for hver pasient i fase I-delen vil være 14 dager (1 behandlingssyklus) der de vil bli gitt én intravenøs dose XB2001 før de får ONIVYDE + Leucovorin l + d racemisk + 5-Fluorouracil kjemoterapibehandling og vurderes for dose Begrensede toksisiteter (DLT). Fase II-delen vil bli implementert etter fullføringen av fase I-delen og erklæringen av MTD. Varigheten av forsøkspersonens deltakelse i den randomiserte, dobbeltblinde, placebokontrollerte fase II-delen av studien er omtrent 28 uker: inkludert en screeningperiode på opptil 30 dager og 24 ukers behandlingsperiode. Alle forsøkspersoner kan fortsette behandlingen med XB2001 i en åpen forlengelse, så lenge de vurderes å være klinisk fordelaktige og ikke har hatt uakseptable toksisiteter.

Studietype

Intervensjonell

Registrering (Faktiske)

76

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Arizona
      • Tucson, Arizona, Forente stater, 85711
        • Arizona Oncology Associates
    • California
      • Burbank, California, Forente stater, 91505
        • Disney Family Cancer Center at Providence St. Joseph Medical Center
      • Cerritos, California, Forente stater, 90703
        • TOI Clinical Research
      • Fullerton, California, Forente stater, 92835
        • Providence St. Joseph Heritage - Fullerton, CA
      • Newport Beach, California, Forente stater, 92663
        • Hoag Memorial Hospital Presbyterian
    • Colorado
      • Grand Junction, Colorado, Forente stater, 81505
        • Grand Valley Oncology
    • Florida
      • Lake Mary, Florida, Forente stater, 32746
        • Sarah Cannon - Florida Cancer Specialists
      • Miami Beach, Florida, Forente stater, 33140
        • Mt. Sinai Comprehensive Cancer Center
      • Sarasota, Florida, Forente stater, 34239
        • Sarasota Memorial Hospital
      • Weston, Florida, Forente stater, 33331
        • Cleveland Clinic of Florida
    • Indiana
      • Goshen, Indiana, Forente stater, 46526
        • Goshen Center for Cancer Care
    • Kansas
      • Merriam, Kansas, Forente stater, 66204
        • Alliance for Multispecialty Research, LLC
    • Louisiana
      • New Orleans, Louisiana, Forente stater, 70121
        • Ochsner Clinic Foundation
    • Michigan
      • Detroit, Michigan, Forente stater, 48201
        • Barbara Ann Karmanos Cancer Institute
      • Farmington Hills, Michigan, Forente stater, 48334
        • Revive Research - Farmington Hills
      • Sterling Heights, Michigan, Forente stater, 48126
        • Revive Research - Sterling Heights
    • Montana
      • Billings, Montana, Forente stater, 59102
        • St. Vincent Frontier Cancer Center
    • New Jersey
      • Florham Park, New Jersey, Forente stater, 07932
        • Summit Medical Group
    • New York
      • Stony Brook, New York, Forente stater, 11794
        • Stony Brook Cancer Center
      • The Bronx, New York, Forente stater, 10461
        • Montefiore Einstein Medical Center
    • Oregon
      • Portland, Oregon, Forente stater, 97213
        • Providence Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forente stater, 15232
        • UPMC Hillman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, Forente stater, 37920
        • University of Tennessee Medical Center Cancer Institute
      • Nashville, Tennessee, Forente stater, 37232
        • Vanderbilt University
      • Nashville, Tennessee, Forente stater, 37203
        • Sarah Cannon - Tennessee Oncology
    • Texas
      • Arlington, Texas, Forente stater, 76012
        • Texas Oncology - Arlington
      • Dallas, Texas, Forente stater, 75230
        • Mary Crowley Cancer Research
    • Utah
      • Ogden, Utah, Forente stater, 84405
        • Community Cancer Trials of Utah
    • Virginia
      • Fairfax, Virginia, Forente stater, 22031
        • Virginia Cancer Specialists
      • Midlothian, Virginia, Forente stater, 23114
        • Bon Secours St. Francis Cancer Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Beskrivelse

Inklusjonskriterier:

  • Histologisk eller cytologisk bekreftet pankreas adenokarsinom i eksokrin bukspyttkjertel som er metastatisk, ikke-opererbar eller tilbakevendende
  • Minst én målbar lesjon i henhold til responsevalueringskriterier i solid tumor V1.1
  • Dokumentert sykdomsprogresjon etter én tidligere gemcitabinbasert behandling ELLER én kombinasjonsbehandling med FOLFIRINOX og gemcitabin
  • Eastern Cooperative Oncology Group (ECOG) ytelse på 0 eller 1 eller Karnofsky ytelsesstatus (KPS) ≥ 70
  • Tilstrekkelig lever-, nyre- og benmargfunksjon

Ekskluderingskriterier:

  • Klinisk signifikant reduksjon i ytelsesstatus (medisinske journaler) innen 2 uker etter tiltenkt første dose administrering
  • Klinisk signifikante GI lidelser
  • Alvorlige arterielle tromboemboliske hendelser mindre enn 6 måneder før inkludering
  • Tidligere strålebehandling av hele hjernen (WBRT)
  • Bevis på hjernemetastaser
  • NYHA klasse III eller IV kongestiv hjertesvikt, ventrikulære arytmier eller ukontrollert blodtrykk (definert som ≥ 160/100 mm Hg)
  • Bruk av sterke CYP3A4-induktorer eller -hemmere og/eller UGT1A1-hemmere innen 14 dager før besøk 1/Baseline-besøk.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Phase I: Dose Escalation Phase

In Phase I (Dose escalation phase), 3 sequential dose levels were administered by participants; 250 mg (dose cohort 1), 500 mg (dose cohort 2), and 1000 mg (dose cohort 3), and traditional 3:3 design was used. Dose-escalation will continue if none of three subjects experience a dose-limiting toxicity (DLT).

After enrollment participants received two treatment cycles (a total of 28 days) in which they were given one intravenous (IV) dose of XB2001 prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Biologisk: Phase I: XB2001 250 mg
Subjects were administered one intravenous (IV) dose of XB2001 250 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navn:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase I: XB2001 500 mg
Subjects were administered one intravenous (IV) dose of XB2001 500 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navn:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase I: XB2001 1000 mg
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navn:
  • anti-IL-1⍺ True Human antibody
Eksperimentell: Phase II: Dose Expansion Phase

In Phase II (dose expansion phase), participants were randomized in 1:1 fashion and received:

  1. XB2001 1000 mg combination with ONIVYDE, Leucovorin, and 5-Fluorouracil
  2. Placebo 1000 mg in combination with ONIVYDE, Leucovorin, and 5-Fluorouracil
Biologisk: Phase II: XB2001 1000 mg
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navn:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase II: Placebo
Subjects were administered one intravenous (IV) dose of placebo 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
To Establish the Maximum Tolerated Dose (MTD) of XB2001 as Measured by Dose-Limiting Toxicity (DLT), in Combination With ONIVYDE + LV + 5-FU Chemotherapy Regimen in Patients With Advanced Pancreatic Cancer.
Tidsramme: 28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).

The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU.

The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II.

A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include:

  1. Inability to deliver all scheduled doses during the 28-day window due to unexpected drug-related toxicity.
  2. Inability to deliver the intended dose of XB2001 due to drug-related toxicity.
28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
Safety and Tolerability of XB2001 in Combination With ONIVYDE + LV + 5-FU
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen.

Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression Free Survival (PFS)
Tidsramme: From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first. Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization. Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.
From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Overall Survival (OS)
Tidsramme: From baseline until death from any cause
OS was defined as the duration from the date of randomization until death irrespective of the cause. Subjects who were alive at the time of analysis were censored at the last known date alive. Subjects without any data after baseline were censored on the randomization day.
From baseline until death from any cause
Objective Response Rate (ORR)
Tidsramme: Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.
Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
Time to Treatment Failure(TTF)
Tidsramme: From baseline until treatment failure assessed up to Visit 13 (Week 24)
TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.
From baseline until treatment failure assessed up to Visit 13 (Week 24)
Number of Serious Adverse Events (SAEs)
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Incidence of Grade 3-4 Diarrhea
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0. Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Duration of Hospitalization
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Plasma Concentration of Natrunix
Tidsramme: Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.

Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile.

Due to reporting limitations on this portal, results from only one time point are reported here.

For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification.
Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
Number of Treatment Cycles
Tidsramme: From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.
From randomization to end of study or study discontinuation for any reasons, up to 24 weeks

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Resultatene av et symptomspørreskjema vil bli oppsummert etter behandlingsarm ved ulike tidspunkt etter infusjon og sammenlignet over tid
Tidsramme: Ved ulike post-infusjonstidspunkter vurdert opp til 22 uker
Poengsummen varierer fra 12 til 48. En høy score representerer dårligere resultat.
Ved ulike post-infusjonstidspunkter vurdert opp til 22 uker
Kardiotoksisitet målt ved antall nødvendige EKG-er og kardiotoksisitetsrelaterte hendelser oppsummert av behandlingsarm og sammenlignet over tid
Tidsramme: Sammenlignet over tid, vurdert opp til 22 uker
Utforskende endepunkt (kun fase 2-del)
Sammenlignet over tid, vurdert opp til 22 uker

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

XBiotech, Inc.

Etterforskere

  • Studiestol: David J Park, Providence St. Joseph Heritage

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

27. mai 2021

Primær fullføring (Faktiske)

26. oktober 2023

Studiet fullført (Faktiske)

10. juni 2025

Datoer for studieregistrering

Først innsendt

24. mars 2021

Først innsendt som oppfylte QC-kriteriene

27. mars 2021

Først lagt ut (Faktiske)

1. april 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

4. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

9. juli 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 2020-PT049

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

Det er foreløpig ikke kjent om det vil være en plan for å gjøre IPD tilgjengelig

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere