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En undersøgelse, der evaluerer kombinationen af ​​Encorafenib og Cetuximab versus Irinotecan/Cetuximab eller Infusions-5-fluorouracil (5-FU)/Folinsyre (FA)/Irinotecan (FOLFIRI)/Cetuximab hos kinesiske patienter med BRAF V600E Mutant Cancer. (NAUTICALCRC)

8. april 2026 opdateret af: Pierre Fabre Medicament

Et multicenter, randomiseret, åbent, 2-arm, fase II-studie med en sikkerhedsindledende fase, der evaluerer kombinationen af ​​Encorafenib og Cetuximab versus Irinotecan/Cetuximab eller Infusions-5-fluorouracil (5-FU)/Folinsyre (FA) /Irinotecan (FOLFIRI)/Cetuximab hos kinesiske patienter med BRAF V600E mutant metastatisk kolorektal cancer.

Encorafenib er i øjeblikket under udvikling (med eller uden binimetinib), i kombination med cetuximab, til behandling af voksne patienter med B-RAF proto-onkogen, serin/threoninkinase V600E mutant (BRAF V600E) metastatisk kolorektal cancer (mCRC), som har modtaget forudgående systemisk terapi.

Studieoversigt

Status

Status

Angiver den aktuelle rekrutteringsstatus eller den udvidede adgangsstatus.
Afsluttet

Betingelser

Betingelser

Den sygdom, lidelse, syndrom, sygdom eller skade, der undersøges. På ClinicalTrials.gov kan tilstande også omfatte andre sundhedsrelaterede problemer, såsom levetid, livskvalitet og sundhedsrisici.

Intervention / Behandling

Intervention / Behandling

En proces eller handling, der er i fokus for en klinisk undersøgelse. Interventioner omfatter lægemidler, medicinsk udstyr, procedurer, vacciner og andre produkter, der enten er til undersøgelse eller allerede er tilgængelige. Interventioner kan også omfatte ikke-invasive tilgange, såsom uddannelse eller ændring af kost og motion.

Undersøgelsestype

Undersøgelsestype

Beskriver karakteren af ​​en klinisk undersøgelse. Undersøgelsestyper omfatter interventionelle undersøgelser (også kaldet kliniske forsøg), observationsundersøgelser (herunder patientregistre) og udvidet adgang.
Interventionel

Tilmelding (Faktiske)

Tilmelding

Antallet af deltagere i en klinisk undersøgelse. Den "forventede" tilmelding er det mål for antallet af deltagere, som forskerne skal bruge til undersøgelsen.
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Fase

Fase

Stadiet af et klinisk forsøg, der studerer et lægemiddel eller et biologisk produkt, baseret på definitioner udviklet af U.S. Food and Drug Administration (FDA). Fasen tager udgangspunkt i undersøgelsens formål, antallet af deltagere og andre karakteristika. Der er fem faser: Tidlig fase 1 (tidligere opført som fase 0), fase 1, fase 2, fase 3 og fase 4. Ikke relevant bruges til at beskrive forsøg uden FDA-definerede faser, herunder forsøg med enheder eller adfærdsmæssige indgreb.
  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiekontakt

Navn og kontaktoplysninger for den person, der kan besvare spørgsmål om tilmelding til en klinisk undersøgelse. Hvert sted, hvor undersøgelsen udføres, kan også have en specifik kontaktperson, som kan være bedre i stand til at besvare disse spørgsmål.

Studiesteder

  • Kina
    • Beijing Municipality
      • Beijing, Beijing Municipality, Kina, 100730
        • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Beijing, Beijing Municipality, Kina, 100036
        • Beijing Cancer Hospital
    • Fujian
      • Fuzhou, Fujian, Kina, 350014
        • Fujian Medical University - Fujian Provincial Cancer Hospital
      • Xiamen, Fujian, Kina, 361001
        • The First Affiliated Hospital of Xiamen University
    • Guangdong
      • Foshan, Guangdong, Kina, 528010
        • The First People's Hospital of Foshan
      • Guangzhou, Guangdong, Kina, 510095
        • Cancer Center of Guangzhou Medical University
      • Guangzhou, Guangdong, Kina, 510655
        • The Sixth Affiliated Hospital Sun Yat-sen University
      • Shantou, Guangdong, Kina, 515041
        • Cancer Hospital Affiliated to Shantou University Medical College
      • Shenzhen, Guangdong, Kina, 518036
        • Peking University Shenzhen Hospital
    • Hebei
      • Baoding, Hebei, Kina, 071000
        • The Affiliated Hospital of Hebei University
    • Heilongjiang
      • Harbin, Heilongjiang, Kina, 150040
        • Harbin Medical University Cancer Hospital
    • Henan
      • Zhengzhou, Henan, Kina, 450052
        • The First Affiliated Hospital of Zhengzhou University
      • Zhengzhou, Henan, Kina, 450008
        • Henan Cancer Hospital
    • Hubei
      • Wuhan, Hubei, Kina, 430071
        • Zhongnan Hospital of Wuhan University
      • Wuhan, Hubei, Kina, 430022
        • Union Hospital Tongji Medical College Huazhong University Of Science And Technology
      • Wuhan, Hubei, Kina, 430030
        • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
    • Hunan
      • Changsha, Hunan, Kina, 410008
        • Xiangya Hospital Central South University
    • Jiangsu
      • Changzhou, Jiangsu, Kina, 213003
        • The First People's Hospital of Changzhou
    • Jiangxi
      • Ganzhou, Jiangxi, Kina, 341001
        • First Affiliated Hospital of Gannan Medical University
      • Nanchang, Jiangxi, Kina, 330006
        • The First Affiliated Hospital of Nanchang University
      • Nanchang, Jiangxi, Kina, 330006
        • The Second Affiliated Hospital of Nanchang University
    • Jilin
      • Changchun, Jilin, Kina, 130021
        • The First Hospital of Jilin University
    • Liaoning
      • Jinzhou, Liaoning, Kina, 121011
        • The First Affiliated Hospital of Jinzhou Medical University
      • Shenyang, Liaoning, Kina, 110001
        • The First Hospital of China Medical University
      • Shenyang, Liaoning, Kina, 110042
        • Liaoning Cancer Hospital & Institute
    • Shaanxi
      • Xi'an, Shaanxi, Kina, 710068
        • Shaanxi Provincial People's Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Kina, 200032
        • Zhongshan Hospital Fudan University
      • Shanghai, Shanghai Municipality, Kina, 200040
        • Huashan Hospital Fudan University
      • Shanghai, Shanghai Municipality, Kina, 200092
        • Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
      • Shanghai, Shanghai Municipality, Kina, 200120
        • Shanghai East Hospital, Tongji University
    • Sichuan
      • Neijiang, Sichuan, Kina, 641000
        • The Second People's Hospital of Neijiang
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, Kina, 300060
        • Tianjin Medical University Cancer Institute and Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310003
        • The First Affiliated Hospital - Zhejiang University School of Medicine
      • Hangzhou, Zhejiang, Kina, 310016
        • Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Berettigelseskriterier

De nøglekrav, som personer, der ønsker at deltage i et klinisk studie, skal opfylde eller de egenskaber, de skal have. Kvalifikationskriterier består af både inklusionskriterier (som er nødvendige for at en person kan deltage i undersøgelsen) og eksklusionskriterier (som forhindrer en person i at deltage). Typer af berettigelseskriterier omfatter, om en undersøgelse accepterer raske frivillige, har alders- eller aldersgruppekrav eller er begrænset af køn.

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier for molekylær præscreening:

Følgende inklusionskriterier skal være opfyldt, for at en deltager er berettiget til at gennemgå molekylær tumorpræscreening:

  • Kinesisk mandlig eller kvindelig deltager med en alder ≥18 år på tidspunktet for informeret samtykke.
  • Histologisk eller cytologisk bekræftet kolorektal cancer (CRC), der er metastatisk.
  • Berettiget til at modtage cetuximab efter kinesisk godkendt etiket med hensyn til tumor Rottesarcoma Viral Onkogen Homolog (RAS) mutationsstatus (dvs. godkendt til rottesarkom viral onkogen homolog vildtype (RAS wt) status).
  • I stand til at levere en tilstrækkelig mængde repræsentativ tumorprøve til central prospektiv laboratorietestning af B-RAF proto-onkogen, serin/threoninkinase (BRAF) mutationsstatus og også retrospektiv RAS wt status og mikrosatellit ustabilitet (MSI) test.

Inklusionskriterier for behandlingsperiode:

Følgende inklusionskriterier skal være opfyldt, for at en deltager er kvalificeret til denne undersøgelse:

  • Kinesisk mandlig eller kvindelig deltager med en alder ≥18 år på tidspunktet for informeret samtykke.
  • Histologisk eller cytologisk bekræftet CRC, der er metastatisk og ikke-opererbar på tidspunktet for studiestart (dvs. ikke egnet til fuldstændig kirurgisk resektion ved screening).
  • Tilstedeværelse af en BRAF V600E-mutation i tumorvæv, som tidligere er bestemt ved et lokalt assay på et hvilket som helst tidspunkt før screening eller af det centrale laboratorium.

BEMÆRK: Andre protokoldefinerede inklusionskriterier kan være gældende

Eksklusionskriterier for molekylær præscreening:

Deltagere, der opfylder et af følgende kriterier, er ikke berettiget til at gennemgå molekylær tumorpræscreening:

  • Forudgående anti-Epidermal Growth Factor Receptor (anti-EGFR) behandling
  • Mere end to tidligere regimer i metastaserende omgivelser.
  • Kendt kontraindikation for at modtage cetuximab eller irinotecan i den planlagte dosis i henhold til den seneste lokale etiket for cetuximab og irinotecan.
  • Kendt historie med Gilberts syndrom eller er kendt for at have en af ​​følgende genotyper: uridin 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 eller UGT1A1*6/*28.
  • Leptomeningeal sygdom.

Eksklusionskriterier for behandlingsperiode:

  • Forudgående behandling med en hvilken som helst Proto-onkogen Serin/threonin-Protein Kinase (RAF)-hæmmer, cetuximab, panitumumab eller andre EGFR-hæmmere.
  • Symptomatisk hjernemetastase.
  • Leptomeningeal sygdom.
  • Brug af naturlægemidler/kosttilskud eller medicin eller fødevarer, der er moderate eller stærke hæmmere eller inducere af cytochrom P450 (CYP)3A4/5 ≤1 uge før start af undersøgelsesintervention.
  • Kendt historie med akut eller kronisk pancreatitis inden for 6 måneder før start af undersøgelsesintervention.

BEMÆRK: Andre protokoldefinerede udelukkelseskriterier kan være gældende

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm

Deltagergruppe / Arm

En gruppe eller undergruppe af deltagere i et klinisk forsøg, der modtager en specifik intervention/behandling eller ingen intervention i henhold til forsøgets protokol.
Intervention / Behandling

Intervention / Behandling

En proces eller handling, der er i fokus for en klinisk undersøgelse. Interventioner omfatter lægemidler, medicinsk udstyr, procedurer, vacciner og andre produkter, der enten er til undersøgelse eller allerede er tilgængelige. Interventioner kan også omfatte ikke-invasive tilgange, såsom uddannelse eller ændring af kost og motion.
Eksperimentel: Encorafenib og cetuximab

Safety Lead-in (SLI) fase:

28 dages cyklusser med encorafenib én gang dagligt (QD) 300 mg (4 x 75 mg oral kapsel) og cetuximab 400 mg/m² startdosis (120-minutters infusion), derefter 250 mg/m² (60-minutters infusion) derefter én gang om ugen

Randomiseret (fase II) fase:

28 dages cyklusser med encorafenib én gang dagligt (QD) 300 mg (4 x 75 mg oral kapsel) og cetuximab 400 mg/m² startdosis (120-minutters infusion), derefter 250 mg/m² (60-minutters infusion) derefter én gang om ugen
Medicin: Encorafenib
oral hård kapsel
Andre navne:
  • LGX818
  • Braftovi®
  • PF-07263896
  • W0090
  • ONO-7702
Medicin: Cetuximab
intravenøs infusion
Andre navne:
  • C225
  • Erbitux®
Eksperimentel: Irinotecan og cetuximab eller FOLFIRI og cetuximab

Randomiseret (fase II) fase: Enten irinotecan og cetuximab eller FOLFIRI og cetuximab i 28 dages cyklusser.

Irinotecan og cetuximab:

  • irinotecan 180 mg/m² (90 minutters intravenøs infusion eller for at studere standarder på stedet) hver 2. uge og
  • cetuximab 400 mg/m² startdosis (120 minutters intravenøs infusion), derefter 250 mg/m² (60 minutters infusion) derefter en gang om ugen

ELLER

FOLFIRI og cetuximab:

  • irinotecan 180 mg/m² (90 minutters intravenøs infusion eller for at studere standarder på stedet) hver 2. uge
  • Folinsyre 400 mg/m² (120 minutters infusion eller for at studere standarder på stedet) eller maksimal dosis tolereret i et tidligere regime hver 2. uge
  • 5-FU 400 mg/m² startdosis bolus (må ikke overstige 15 minutter), derefter 1200 mg/m²/dag × 2 dage (i alt 2400 mg/m² over 46 til 48 timer) kontinuerlig infusion eller maksimal dosis tolereret i et tidligere regime hver 2. uge og
  • cetuximab 400 mg/m² startdosis (120 minutters intravenøs infusion), derefter 250 mg/m² (60 minutters infusion) derefter en gang om ugen
Medicin: Encorafenib
oral hård kapsel
Andre navne:
  • LGX818
  • Braftovi®
  • PF-07263896
  • W0090
  • ONO-7702
Medicin: Cetuximab
intravenøs infusion
Andre navne:
  • C225
  • Erbitux®
Medicin: FOLFIRI

Kombination af:

irinotecan (også kendt som: Camptosar, Camptothecin-11 og CPT-11) intravenøs infusion, folinsyre (også kendt som: 5-formyltetrahydrofolinsyre og leucovorin) intravenøs infusion og 5-FU (også kendt som; fluorouracil) intravenøs bolus /intravenøs infusion

Andre navne:
  • Folinsyre + Fluorouracil + Irinotecan

Hvad måler undersøgelsen?

Primære resultatmål

Primære resultatmål

I et klinisk studies protokol er det planlagte resultatmål, der er det vigtigste for at evaluere effekten af ​​en intervention/behandling. De fleste kliniske undersøgelser har ét primært resultatmål, men nogle har mere end ét.
Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Tidsramme: Cycle 1 (up to 28 days)
DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm.
Cycle 1 (up to 28 days)
Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date
Tidsramme: From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis
Tidsramme: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks

Sekundære resultatmål

Sekundære resultatmål

I en klinisk undersøgelses protokol er et planlagt resultatmål, der ikke er lige så vigtigt som det primære resultatmål for at evaluere effekten af ​​en intervention, men som stadig er af interesse. De fleste kliniske undersøgelser har mere end ét sekundært resultatmål.
Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
cORR as determined by investigator assessment per RECIST version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Duration of Response (DOR) Per BICR
Tidsramme: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Duration of Response (DOR) Per Investigator
Tidsramme: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment
Tidsramme: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day". Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Tidsramme: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting TEAEs were reported in this outcome measure.
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Serious TEAEs
Tidsramme: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability. Number of participants reporting serious TEAEs were reported in this outcome measure.
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Tidsramme: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
An AE is any untoward medical occurrence in a participant, whether or not considered related to the study intervention. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure.
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline. The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline. The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities
Tidsramme: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment. [1] The category "Other" includes all other dermatological findings identified during examination (e.g. rash acneiform, skin hyperpigmentation...).
From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale. The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Progression-free Survival (PFS) by Investigator
Tidsramme: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
PFS was defined as the time from the date of randomization to the earliest documented date of PD as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per BICR
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
cORR as determined by investigator assessment per RECIST Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per BICR
Tidsramme: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Tidsramme: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per BICR
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by BICR per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Tidsramme: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by investigator assesment per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per BICR
Tidsramme: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by BICR per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Tidsramme: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by investigator assessment per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Overall Survival (OS)
Tidsramme: From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
OS was defined as time from randomization until date of death due to any cause.
From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Overall Duration of Exposure to Study Treatment
Tidsramme: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day". Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Tidsramme: Day 1 until 30 days after study intervention discontinuation
A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting TEAEs were reported in this outcome measure.
Day 1 until 30 days after study intervention discontinuation
Randomized Phase 2: Number of Participants With Serious TEAEs
Tidsramme: Day 1 until 30 days after study intervention discontinuation
A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability. Number of participants reporting serious TEAEs were reported in this outcome measure.
Day 1 until 30 days after study intervention discontinuation
Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities
Tidsramme: Day 1 until 30 days after last dose of study treatment
Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline. The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Tidsramme: Day 1 until 30 days after last dose of study treatment
Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline. The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Tidsramme: Day 1 until 30 days after last dose of study treatment
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Tidsramme: Day 1 until 30 days after last dose of study treatment
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities
Tidsramme: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment. [1] All other dermatological findings identified during examination (e.g. rash acneiform, skin hyperpigmentation...).
From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Tidsramme: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale. The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death. [1] Participants with no assessment of ECOG in the time frame.
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Time to Definitive Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) Questionnaire Scores
Tidsramme: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire consisted of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale. Each scale in the questionnaire was scored (0 to 100). High scores represented a high health/quality of life. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Time to Definitive Deterioration in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire
Tidsramme: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) consisted of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system consisted of five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each was rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that described the participant's health state. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Time to Definitive Deterioration in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) Questionnaire
Tidsramme: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) was a validated quality of life questionnaire for patient reported outcome assessment. The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) consisted of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale. Higher score reflects a better quality of life. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Evolution in the Patient Global Impression of Change (PGIC) Questionnaire
Tidsramme: Cycle 2 Day 1 until 30 days safety follow-up
The Patient Global Impression of Change (PGIC) questionnaire is a scale often used to anchor and characterize participant reported outcome (PRO) findings. This consisted of questions that asked participants to evaluate their colorectal cancer symptoms since starting study intervention according to a seven-point verbal rating scale: 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse. Completions of questionnaire are summarized per treatment group and study visits. Number of participants analyzed correspond to the actual number of participants who completed the questionnaire at the corresponding visit.
Cycle 2 Day 1 until 30 days safety follow-up
Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Serum Concentrations of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Tidsramme: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.

Andre resultatmål

Andre resultatmål

For kliniske forsøg en planlagt måling beskrevet i protokollen, der bruges til at bestemme effekten af ​​en intervention/behandling på deltagerne. Til observationsstudier, en måling eller observation, der bruges til at beskrive mønstre af sygdomme eller egenskaber eller sammenhænge med eksponeringer, risikofaktorer eller behandling. Typer af resultatmål omfatter primært resultatmål og sekundært resultatmål.
Resultatmål
Tidsramme
Randomiseret fase 2: Ændringer fra baseline i blodkarcinoembryonalt antigen (CEA) og kræftantigen 19-9 (CA19-9) i begyndelsen af ​​hver cyklus og i slutningen af ​​behandlingen
Tidsramme: Screening (dag -28 til -1) frem til studiets afslutning, ca. fra 12 til 29 måneder
Screening (dag -28 til -1) frem til studiets afslutning, ca. fra 12 til 29 måneder
Randomiseret fase 2: Mikrosatellit-instabilitet (MSI) status i formalinfikserede og paraffinindlejrede (FFPE) prøver ved brug af etablerede polymerasekædereaktions (PCR) assays i tumorprøve versus kimlinjekontrol ved screening
Tidsramme: Screening (dag -28 til dag -1)
Screening (dag -28 til dag -1)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Sponsor

Den organisation eller person, der igangsætter undersøgelsen, og som har myndighed og kontrol over undersøgelsen.
Pierre Fabre Medicament

Samarbejdspartnere

Samarbejdspartnere

En anden organisation end sponsoren, der yder støtte til en klinisk undersøgelse. Denne støtte kan omfatte aktiviteter relateret til finansiering, design, implementering, dataanalyse eller rapportering.
Merck KGaA, Darmstadt, Germany

Efterforskere

Efterforskere

En forsker involveret i et klinisk studie. Beslægtede termer omfatter stedets principal investigator, site sub-investigator, studieformand, undersøgelsesleder og undersøgelseshovedinvestigator.
  • Ledende efterforsker: Shen Lin, MD, Peking University Cancer Hospital & Institute

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

Studiestart

Den faktiske dato, hvor den første deltager blev tilmeldt en klinisk undersøgelse. Den "forventede" undersøgelses startdato er den dato, som forskerne tror vil være undersøgelsens startdato.
14. september 2021

Primær færdiggørelse (Faktiske)

Primær færdiggørelse

Den dato, hvor den sidste deltager i et klinisk studie blev undersøgt eller modtog en intervention for at indsamle endelige data for det primære resultatmål. Hvorvidt det kliniske studie sluttede i henhold til protokollen eller blev afsluttet, påvirker ikke denne dato. For kliniske undersøgelser med mere end ét primært resultatmål med forskellige afslutningsdatoer refererer dette udtryk til den dato, hvor dataindsamlingen er afsluttet for alle de primære resultatmål. Den "forventede" primære afslutningsdato er den dato, som forskerne tror vil være den primære afslutningsdato for undersøgelsen.
19. december 2023

Studieafslutning (Faktiske)

Studieafslutning

Den dato, hvor den sidste deltager i et klinisk studie blev undersøgt eller modtog en intervention/behandling for at indsamle endelige data for de primære resultatmål, sekundære udfaldsmål og uønskede hændelser (det vil sige den sidste deltagers sidste besøg). Den "forventede" undersøgelses afslutningsdato er den dato, som forskerne tror vil være undersøgelsens afslutningsdato.
7. december 2024

Datoer for studieregistrering

Først indsendt

Først indsendt

Den dato, hvor undersøgelsens sponsor eller investigator første gang indsendte en undersøgelsespost til ClinicalTrials.gov. Der er typisk en forsinkelse på et par dage mellem den første indsendte dato og postens tilgængelighed på ClinicalTrials.gov (den første offentliggjorte dato).
30. april 2021

Først indsendt, der opfyldte QC-kriterier

Først indsendt, der opfyldte QC-kriterier

Den dato, hvor undersøgelsens sponsor eller investigator første gang indsender en undersøgelsespost, der er i overensstemmelse med National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgangskriterier. Sponsoren eller investigatoren skal muligvis revidere og indsende en undersøgelsespost en eller flere gange, før NLM's kvalitetskontrolkriterier er opfyldt. Det er sponsorens eller investigatorens ansvar at sikre, at undersøgelsesposten er i overensstemmelse med NLM QC-gennemgangskriterierne.
5. august 2021

Først opslået (Faktiske)

Først opslået

Datoen, hvor undersøgelsesposten først var tilgængelig på ClinicalTrials.gov efter National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgang er afsluttet. Der er typisk en forsinkelse på et par dage mellem den dato, hvor undersøgelsens sponsor eller investigator indsendte undersøgelsesposten, og den første offentliggjorte dato.
13. august 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

Sidste opdatering sendt

Den seneste dato, hvor ændringer i en undersøgelsespost blev gjort tilgængelig på ClinicalTrials.gov. Der kan være en forsinkelse mellem det tidspunkt, hvornår ændringerne blev indsendt til ClinicalTrials.gov af undersøgelsens sponsor eller investigator (datoen for sidste opdatering afsendt) og den sidste opdatering, der blev sendt.
30. april 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

Den seneste dato, hvor undersøgelsens sponsor eller investigator indsendte ændringer til en undersøgelsespost, der er i overensstemmelse med National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgangskriterier. Det er sponsorens eller investigatorens ansvar at sikre, at undersøgelsesposten er i overensstemmelse med NLM QC-gennemgangskriterierne.
8. april 2026

Sidst verificeret

Sidst verificeret

Den seneste dato, hvor undersøgelsens sponsor eller investigator bekræftede oplysningerne om en klinisk undersøgelse på ClinicalTrials.gov som nøjagtige og aktuelle. Hvis en undersøgelse med rekrutteringsstatus som rekruttering; rekrutterer endnu ikke; eller aktiv, ikke rekruttering er ikke blevet bekræftet inden for de seneste 2 år, er undersøgelsens rekrutteringsstatus vist som ukendt.
1. februar 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

Andre undersøgelses-id-numre

Andre identifikatorer eller ID-numre end NCT-nummeret, der er tildelt til en klinisk undersøgelse af undersøgelsens sponsor, finansieringsgivere eller andre. Disse numre kan omfatte unikke identifikatorer fra andre forsøgsregistre og National Institutes of Health-bevillingsnumre.
  • W00090GE202

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Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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