Uno studio che valuta la combinazione di encorafenib e cetuximab rispetto a irinotecan/cetuximab o 5-fluorouracile infusionale (5-FU)/acido folinico (FA)/irinotecan (FOLFIRI)/cetuximab in pazienti cinesi con carcinoma colorettale metastatico con mutazione BRAF V600E. (NAUTICALCRC)
8 aprile 2026 aggiornato da: Pierre Fabre Medicament
Uno studio multicentrico, randomizzato, in aperto, a 2 bracci, di fase II con una fase introduttiva di sicurezza che valuta la combinazione di encorafenib e cetuximab rispetto a irinotecan/cetuximab o 5-fluorouracile infusionale (5-FU)/acido folinico (FA) /Irinotecan (FOLFIRI)/Cetuximab in pazienti cinesi con carcinoma colorettale metastatico con mutazione BRAF V600E.
Encorafenib è attualmente in fase di sviluppo (con o senza binimetinib), in combinazione con cetuximab, per il trattamento di pazienti adulti con carcinoma colorettale metastatico (mCRC) del proto-oncogene B-RAF, mutante serina/treonina chinasi V600E (BRAF V600E), che hanno ricevuto una precedente terapia sistemica.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
107
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Beijing Municipality
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Beijing, Beijing Municipality, Cina, 100730
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing Municipality, Cina, 100036
- Beijing Cancer Hospital
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Fujian
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Fuzhou, Fujian, Cina, 350014
- Fujian Medical University - Fujian Provincial Cancer Hospital
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Xiamen, Fujian, Cina, 361001
- The First Affiliated Hospital of Xiamen University
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Guangdong
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Foshan, Guangdong, Cina, 528010
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, Cina, 510095
- Cancer Center of Guangzhou Medical University
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Guangzhou, Guangdong, Cina, 510655
- The Sixth Affiliated Hospital Sun Yat-sen University
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Shantou, Guangdong, Cina, 515041
- Cancer Hospital Affiliated to Shantou University Medical College
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Shenzhen, Guangdong, Cina, 518036
- Peking University Shenzhen Hospital
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Hebei
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Baoding, Hebei, Cina, 071000
- The Affiliated Hospital of Hebei University
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Heilongjiang
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Harbin, Heilongjiang, Cina, 150040
- Harbin Medical University Cancer Hospital
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Henan
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Zhengzhou, Henan, Cina, 450052
- The First Affiliated Hospital of Zhengzhou University
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Zhengzhou, Henan, Cina, 450008
- Henan Cancer Hospital
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Hubei
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Wuhan, Hubei, Cina, 430071
- Zhongnan Hospital of Wuhan University
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Wuhan, Hubei, Cina, 430022
- Union Hospital Tongji Medical College Huazhong University Of Science And Technology
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Wuhan, Hubei, Cina, 430030
- Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
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Hunan
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Changsha, Hunan, Cina, 410008
- Xiangya Hospital Central South University
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Jiangsu
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Changzhou, Jiangsu, Cina, 213003
- The First People's Hospital of Changzhou
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Jiangxi
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Ganzhou, Jiangxi, Cina, 341001
- First Affiliated Hospital of Gannan Medical University
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Nanchang, Jiangxi, Cina, 330006
- The First Affiliated Hospital of Nanchang University
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Nanchang, Jiangxi, Cina, 330006
- The Second Affiliated Hospital of Nanchang University
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Jilin
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Changchun, Jilin, Cina, 130021
- The First Hospital of Jilin University
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Liaoning
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Jinzhou, Liaoning, Cina, 121011
- The First Affiliated Hospital of Jinzhou Medical University
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Shenyang, Liaoning, Cina, 110001
- The First Hospital of China Medical University
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Shenyang, Liaoning, Cina, 110042
- Liaoning Cancer Hospital & Institute
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Shaanxi
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Xi'an, Shaanxi, Cina, 710068
- Shaanxi Provincial People's Hospital
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Cina, 200032
- Zhongshan Hospital Fudan University
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Shanghai, Shanghai Municipality, Cina, 200040
- Huashan Hospital Fudan University
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Shanghai, Shanghai Municipality, Cina, 200092
- Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
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Shanghai, Shanghai Municipality, Cina, 200120
- Shanghai East Hospital, Tongji University
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Sichuan
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Neijiang, Sichuan, Cina, 641000
- The Second People's Hospital of Neijiang
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Cina, 300060
- Tianjin Medical University Cancer Institute and Hospital
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Zhejiang
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Hangzhou, Zhejiang, Cina, 310003
- The First Affiliated Hospital - Zhejiang University School of Medicine
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Hangzhou, Zhejiang, Cina, 310016
- Sir Run Run Shaw Hospital - Zhejiang University School of Medicine
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Descrizione
Criteri di inclusione per il prescreening molecolare:
I seguenti criteri di inclusione devono essere soddisfatti affinché un partecipante sia idoneo a sottoporsi a pre-screening del tumore molecolare:
- Partecipante maschio o femmina cinese con età ≥18 anni al momento del consenso informato.
- Cancro del colon-retto (CRC) confermato istologicamente o citologicamente che è metastatico.
- Idoneo a ricevere cetuximab secondo l'etichetta cinese approvata per quanto riguarda lo stato di mutazione dell'omologo virale dell'oncogene (RAS) del sarcoma del ratto (ad es. approvato per lo stato Rat Sarcoma Viral Oncogene Homologue Wild Type (RAS wt).
- In grado di fornire una quantità sufficiente di campioni tumorali rappresentativi per i test di laboratorio prospettici centrali del proto-oncogene B-RAF, dello stato di mutazione della serina/treonina chinasi (BRAF) e anche per il test retrospettivo dello stato RAS wt e dell'instabilità dei microsatelliti (MSI).
Criteri di inclusione per il periodo di trattamento:
I seguenti criteri di inclusione devono essere soddisfatti affinché un partecipante sia idoneo per questo studio:
- Partecipante maschio o femmina cinese con età ≥18 anni al momento del consenso informato.
- CRC confermato istologicamente o citologicamente che è metastatico e non resecabile al momento dell'ingresso nello studio (es. non adatto per la resezione chirurgica completa allo screening).
- Presenza di una mutazione BRAF V600E nel tessuto tumorale precedentemente determinata da un test locale in qualsiasi momento prima dello screening o dal laboratorio centrale.
NOTA: potrebbero essere applicati altri criteri di inclusione definiti dal protocollo
Criteri di esclusione per il prescreening molecolare:
I partecipanti che soddisfano uno dei seguenti criteri non sono idonei a sottoporsi a pre-screening del tumore molecolare:
- Precedente trattamento con il recettore del fattore di crescita epidermico (anti-EGFR).
- Più di due regimi precedenti nel contesto metastatico.
- Controindicazione nota a ricevere cetuximab o irinotecan alla dose pianificata secondo la più recente etichetta locale di cetuximab e irinotecan.
- Storia nota della sindrome di Gilbert o presenza nota di uno dei seguenti genotipi: uridina 5'-difosfo-glucuronosiltransferasi (UGT)1A1*6/*6, UGT1A1*28/*28 o UGT1A1*6/*28.
- Malattia leptomeningea.
Criteri di esclusione per il periodo di trattamento:
- Precedente trattamento con qualsiasi inibitore del Proto-oncogene serina/treonina-proteina chinasi (RAF), cetuximab, panitumumab o altri inibitori dell'EGFR.
- Metastasi cerebrali sintomatiche.
- Malattia leptomeningea.
- Uso di farmaci/integratori a base di erbe o farmaci o alimenti che sono inibitori o induttori moderati o forti del citocromo P450 (CYP) 3A4/5 ≤1 settimana prima dell'inizio dell'intervento dello studio.
- Storia nota di pancreatite acuta o cronica entro 6 mesi prima dell'inizio dell'intervento dello studio.
NOTA: potrebbero essere applicati altri criteri di esclusione definiti dal protocollo
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Encorafenib e cetuximab
Fase di sicurezza Lead-in (SLI): Cicli di 28 giorni di encorafenib una volta al giorno (QD) 300 mg (4 x 75 mg capsule orali) e cetuximab 400 mg/m² dose iniziale (infusione di 120 minuti), quindi 250 mg/m² (infusione di 60 minuti) successivamente una volta alla settimana Fase randomizzata (fase II): Cicli di 28 giorni di encorafenib una volta al giorno (QD) 300 mg (4 x 75 mg capsule orali) e cetuximab 400 mg/m² dose iniziale (infusione di 120 minuti), quindi 250 mg/m² (infusione di 60 minuti) successivamente una volta alla settimana |
capsula rigida orale
Altri nomi:
infusione endovenosa
Altri nomi:
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Sperimentale: Irinotecan e cetuximab o FOLFIRI e cetuximab
Fase randomizzata (fase II): o irinotecan e cetuximab o FOLFIRI e cetuximab in cicli di 28 giorni. Irinotecan e cetuximab:
O FOLFIRI e cetuximab:
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capsula rigida orale
Altri nomi:
infusione endovenosa
Altri nomi:
Combinazione di: irinotecan (noto anche come: Camptosar, Camptothecin-11 e CPT-11) infusione endovenosa, acido folinico (noto anche come: acido 5-formil tetraidrofolico e leucovorin) infusione endovenosa e bolo endovenoso di 5-FU (noto anche come; fluorouracile) /infusione endovenosa
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Lasso di tempo: Cycle 1 (up to 28 days)
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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.
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Cycle 1 (up to 28 days)
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date
Lasso di tempo: 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
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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.
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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
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis
Lasso di tempo: 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
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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.
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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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
Lasso di tempo: 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
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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.
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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
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator
Lasso di tempo: 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
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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.
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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
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Safety Lead-in Phase: Duration of Response (DOR) Per BICR
Lasso di tempo: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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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.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Duration of Response (DOR) Per Investigator
Lasso di tempo: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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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.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment
Lasso di tempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Lasso di tempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Serious TEAEs
Lasso di tempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Lasso di tempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
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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.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities
Lasso di tempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Lasso di tempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Lasso di tempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Lasso di tempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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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.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities
Lasso di tempo: 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
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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...).
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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
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Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Lasso di tempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
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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.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
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Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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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.
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Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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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.
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Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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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.
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Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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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.
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Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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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.
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Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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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.
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Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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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.
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Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Lasso di tempo: 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.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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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.
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Randomized Phase 2: Progression-free Survival (PFS) by Investigator
Lasso di tempo: 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
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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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
|
Altre misure di risultato
Misura del risultato |
Lasso di tempo |
|---|---|
|
Fase 2 randomizzata: variazioni rispetto al basale dell'antigene carcinoembrionale (CEA) e dell'antigene tumorale 19-9 (CA19-9) all'inizio di ciascun ciclo e alla fine del trattamento
Lasso di tempo: Screening (giorno da -28 a -1) fino al completamento dello studio, approssimativamente da 12 a 29 mesi
|
Screening (giorno da -28 a -1) fino al completamento dello studio, approssimativamente da 12 a 29 mesi
|
|
Fase 2 randomizzata: stato di instabilità dei microsatelliti (MSI) in campioni fissati in formalina e inclusi in paraffina (FFPE) utilizzando test di reazione a catena della polimerasi (PCR) consolidati nel campione tumorale rispetto al controllo della linea germinale allo screening
Lasso di tempo: Screening (dal giorno -28 al giorno -1)
|
Screening (dal giorno -28 al giorno -1)
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Shen Lin, MD, Peking University Cancer Hospital & Institute
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
14 settembre 2021
Completamento primario (Effettivo)
19 dicembre 2023
Completamento dello studio (Effettivo)
7 dicembre 2024
Date di iscrizione allo studio
Primo inviato
30 aprile 2021
Primo inviato che soddisfa i criteri di controllo qualità
5 agosto 2021
Primo Inserito (Effettivo)
13 agosto 2021
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
30 aprile 2026
Ultimo aggiornamento inviato che soddisfa i criteri QC
8 aprile 2026
Ultimo verificato
1 febbraio 2026
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per sede
- Neoplasie
- Malattie intestinali
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie dell'apparato digerente
- Malattie gastrointestinali
- Neoplasie intestinali
- Malattie del retto
- Malattie del colon
- Neoplasie colorettali
- Aminoacidi, peptidi e proteine
- Proteine
- Composti eterociclici, 1-anello
- Composti eterociclici
- Composti eterociclici, 2 anelli
- Composti eterociclici, anello fuso
- Camptothecin
- Alcaloidi
- Enzimi e coenzimi
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Pirimidine
- Formyltetraidrofolates
- Tetraidrofolati
- Acido folico
- Pterins
- Pteridine
- Uracile
- Pirimidinoni
- Coenzimi
- Irinotecano
- Cetuximab
- Fluorouracile
- Leucovorina
- encorafenib
- Protocollo IFL
Altri numeri di identificazione dello studio
- W00090GE202
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
prodotto fabbricato ed esportato dagli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .