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Een studie ter evaluatie van de combinatie van encorafenib en cetuximab versus irinotecan/cetuximab of infuus 5-fluorouracil (5-FU)/folinezuur (FA)/irinotecan (FOLFIRI)/cetuximab bij Chinese patiënten met BRAF V600E-gemuteerde gemetastaseerde colorectale kanker. (NAUTICALCRC)

8 april 2026 bijgewerkt door: Pierre Fabre Medicament

Een multicenter, gerandomiseerde, open-label, 2-armige, fase II-studie met een veiligheidsaanloopfase ter evaluatie van de combinatie van encorafenib en cetuximab versus irinotecan/cetuximab of infuus 5-fluorouracil (5-FU)/foliumzuur (FA) /Irinotecan (FOLFIRI)/Cetuximab bij Chinese patiënten met BRAF V600E-gemuteerde gemetastaseerde colorectale kanker.

Encorafenib wordt momenteel ontwikkeld (met of zonder binimetinib), in combinatie met cetuximab, voor de behandeling van volwassen patiënten met B-RAF proto-oncogeen, serine/threonine kinase V600E mutant (BRAF V600E) gemetastaseerde colorectale kanker (mCRC), die eerdere systemische therapie hebben gekregen.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

107

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Opnamecriteria voor moleculaire prescreening:

Een deelnemer moet aan de volgende inclusiecriteria voldoen om in aanmerking te komen voor prescreening op moleculaire tumoren:

  • Chinese mannelijke of vrouwelijke deelnemer met een leeftijd van ≥18 jaar op het moment van geïnformeerde toestemming.
  • Histologisch of cytologisch bevestigde colorectale kanker (CRC) die metastatisch is.
  • Komt in aanmerking voor cetuximab volgens Chinees goedgekeurd label met betrekking tot tumor Rat Sarcoom Viral Oncogene Homologue (RAS) mutatiestatus (d.w.z. goedgekeurd voor rat sarcoom viraal oncogeen homoloog wild type (RAS wt) status).
  • In staat om een ​​voldoende hoeveelheid representatief tumorspecimen te leveren voor centrale prospectieve laboratoriumtesten van B-RAF proto-oncogen, serine/threoninekinase (BRAF)-mutatiestatus en ook retrospectieve RAS wt-status en Microsatellite Instability (MSI)-testen.

Opnamecriteria voor behandelingsperiode:

Een deelnemer moet aan de volgende inclusiecriteria voldoen om in aanmerking te komen voor deze studie:

  • Chinese mannelijke of vrouwelijke deelnemer met een leeftijd van ≥18 jaar op het moment van geïnformeerde toestemming.
  • Histologisch of cytologisch bevestigd CRC dat metastatisch en inoperabel is op het moment van aanvang van het onderzoek (d.w.z. niet geschikt voor volledige chirurgische resectie bij screening).
  • Aanwezigheid van een BRAF V600E-mutatie in tumorweefsel, eerder bepaald door een lokale assay op enig moment voorafgaand aan de screening of door het centrale laboratorium.

OPMERKING: Andere in het protocol gedefinieerde opnamecriteria kunnen van toepassing zijn

Uitsluitingscriteria voor moleculaire prescreening:

Deelnemers die aan een van de volgende criteria voldoen, komen niet in aanmerking voor prescreening op moleculaire tumoren:

  • Eerdere behandeling met anti-epidermale groeifactorreceptor (anti-EGFR).
  • Meer dan twee eerdere regimes in de metastatische setting.
  • Bekende contra-indicatie om cetuximab of irinotecan te krijgen in de geplande dosis volgens het meest recente lokale label van cetuximab en irinotecan.
  • Bekende voorgeschiedenis van het syndroom van Gilbert of waarvan bekend is dat het een van de volgende genotypen heeft: uridine 5'-difosfo-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 of UGT1A1*6/*28.
  • Leptomeningeale ziekte.

Uitsluitingscriteria voor behandelingsperiode:

  • Voorafgaande behandeling met een Proto-oncogene serine/threonine-proteïnekinase (RAF)-remmer, cetuximab, panitumumab of andere EGFR-remmers.
  • Symptomatische hersenmetastasen.
  • Leptomeningeale ziekte.
  • Gebruik van kruidengeneesmiddelen/-supplementen of medicijnen of voedingsmiddelen die matige of sterke remmers of inductoren zijn van cytochroom P450 (CYP)3A4/5 ≤1 week voor aanvang van de studie-interventie.
  • Bekende voorgeschiedenis van acute of chronische pancreatitis binnen 6 maanden voor aanvang van de onderzoeksinterventie.

OPMERKING: Er kunnen andere in het protocol gedefinieerde uitsluitingscriteria van toepassing zijn

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Encorafenib en cetuximab

Safety Lead-in (SLI) fase:

28-daagse cycli van encorafenib eenmaal daags (QD) 300 mg (4 x 75 mg orale capsule) en cetuximab 400 mg/m² aanvangsdosis (120 minuten infusie), daarna 250 mg/m² (60 minuten infusie) daarna eenmaal per week

Gerandomiseerde (fase II) fase:

28-daagse cycli van encorafenib eenmaal daags (QD) 300 mg (4 x 75 mg orale capsule) en cetuximab 400 mg/m² aanvangsdosis (120 minuten infusie), daarna 250 mg/m² (60 minuten infusie) daarna eenmaal per week
Geneesmiddel: Encorafenib
orale harde capsule
Andere namen:
  • LGX818
  • Bratovi®
  • PF-07263896
  • W0090
  • ONO-7702
Geneesmiddel: Cetuximab
intraveneuze infusie
Andere namen:
  • C225
  • Erbitux®
Experimenteel: Irinotecan en cetuximab of FOLFIRI en cetuximab

Gerandomiseerde (fase II) fase: irinotecan en cetuximab of FOLFIRI en cetuximab in cycli van 28 dagen.

Irinotecan en cetuximab:

  • irinotecan 180 mg/m² (90 minuten intraveneus infuus of volgens studieplaatsstandaarden) elke 2 weken en
  • cetuximab 400 mg/m² aanvangsdosis (120 minuten intraveneuze infusie), daarna 250 mg/m² (60 minuten infusie) daarna eenmaal per week

OF

FOLFIRI en cetuximab:

  • irinotecan 180 mg/m² (90 minuten intraveneuze infusie of volgens de standaarden van de studieplaats) elke 2 weken
  • Folinezuur 400 mg/m² (infusie van 120 minuten of volgens de standaarden van de studieplaats) of maximale dosis die werd getolereerd in een eerder regime om de 2 weken
  • 5-FU 400 mg/m² startdosis bolus (niet langer dan 15 minuten), daarna 1200 mg/m²/dag × 2 dagen (totaal 2400 mg/m² over 46 tot 48 uur) continu infuus of maximale dosis getolereerd in een eerder regime elke 2 weken en
  • cetuximab 400 mg/m² aanvangsdosis (120 minuten intraveneuze infusie), daarna 250 mg/m² (60 minuten infusie) daarna eenmaal per week
Geneesmiddel: Encorafenib
orale harde capsule
Andere namen:
  • LGX818
  • Bratovi®
  • PF-07263896
  • W0090
  • ONO-7702
Geneesmiddel: Cetuximab
intraveneuze infusie
Andere namen:
  • C225
  • Erbitux®
Geneesmiddel: FOLFIRI

Combinatie van:

irinotecan (ook bekend als: Camptosar, Camptothecin-11 en CPT-11) intraveneuze infusie, folinezuur (ook bekend als: 5-formyltetrahydrofoliumzuur en leucovorine) intraveneuze infusie en 5-FU (ook bekend als; fluorouracil) intraveneuze bolus /intraveneuze infusie

Andere namen:
  • Folinezuur + Fluorouracil + Irinotecan

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.

Andere uitkomstmaten

Uitkomstmaat
Tijdsspanne
Gerandomiseerde fase 2: veranderingen ten opzichte van baseline in carcino-embryonaal antigeen (CEA) en kankerantigeen 19-9 (CA19-9) in het bloed aan het begin van elke cyclus en aan het einde van de behandeling
Tijdsspanne: Screening (dag -28 tot -1) tot voltooiing van de studie, ongeveer van 12 tot 29 maanden
Screening (dag -28 tot -1) tot voltooiing van de studie, ongeveer van 12 tot 29 maanden
Gerandomiseerde fase 2: status van microsatellietinstabiliteit (MSI) in in formaline gefixeerde en in paraffine ingebedde (FFPE)-monsters met behulp van gevestigde polymerasekettingreactie-assays (PCR) in tumormonster versus kiembaancontrole bij screening
Tijdsspanne: Screening (dag -28 tot dag -1)
Screening (dag -28 tot dag -1)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Pierre Fabre Medicament

Medewerkers

Merck KGaA, Darmstadt, Germany

Onderzoekers

  • Hoofdonderzoeker: Shen Lin, MD, Peking University Cancer Hospital & Institute

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

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Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

14 september 2021

Primaire voltooiing (Werkelijk)

19 december 2023

Studie voltooiing (Werkelijk)

7 december 2024

Studieregistratiedata

Eerst ingediend

30 april 2021

Eerst ingediend dat voldeed aan de QC-criteria

5 augustus 2021

Eerst geplaatst (Werkelijk)

13 augustus 2021

Updates van studierecords

Laatste update geplaatst (Werkelijk)

30 april 2026

Laatste update ingediend die voldeed aan QC-criteria

8 april 2026

Laatst geverifieerd

1 februari 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • W00090GE202

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

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