BRAF V600EPhase 2NAUTICALCRCNCT05004350
A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.
A Phase 2 study testing Encorafenib, Cetuximab and FOLFIRI in people with BRAF V600E and Metastatic Colorectal Cancer, run by Pierre Fabre Medicament at 34 sites in China.
Trial summary
Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- BRAF V600E, Metastatic Colorectal Cancer
- What is being tested?
- Encorafenib, Cetuximab and FOLFIRI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 34 sitesChina
- Study dates
- 14 Sep 2021to 7 Dec 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The following inclusion criteria must be met for a participant to be eligible to undergo molecular tumor prescreening:
- Chinese male or female participant with age ≥18 years at the time of informed consent.
- Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic.
- Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma Viral Oncogene Homologue Wild Type(RAS wt) status).
- Able to provide a sufficient amount of representative tumor specimen for central prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF) mutation status and also retrospective RAS wt status and Microsatellite Instability (MSI) testing.
- The following inclusion criteria must be met for a participant to be eligible for this study:
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- Chinese male or female participant with age ≥18 years at time of informed consent.
- Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening).
- Presence of a BRAF V600E mutation in tumor tissue previously determined by a local assay at any time before screening or by the central laboratory.
- NOTE: Other protocol defined Inclusion criteria may apply
Who cannot join
- Participants meeting any of the following criteria are not eligible to undergo molecular tumor prescreening:
- Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment
- More than two prior regimens in the metastatic setting.
- Known contraindication to receive cetuximab or irinotecan at the planned dose according to the most recent cetuximab and irinotecan local label.
- Known history of Gilbert's syndrome or is known to have any of the following genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 or UGT1A1*6/*28.
- Leptomeningeal disease.
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- Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF) inhibitor, cetuximab, panitumumab or other EGFR inhibitors.
- Symptomatic brain metastasis.
- Leptomeningeal disease.
- Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 ≤1 week before the start of study intervention.
- Known history of acute or chronic pancreatitis within 6 months before the start of study intervention.
- NOTE: Other protocol defined Exclusion criteria may apply
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
China34 sites
The Affiliated Hospital of Hebei University
Baoding, Hebei, 071000
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100036
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100730
The First Hospital of Jilin University
Changchun, Jilin, 130021
Xiangya Hospital Central South University
Changsha, Hunan, 410008
The First People's Hospital of Changzhou
Changzhou, Jiangsu, 213003
The First People's Hospital of Foshan
Foshan, Guangdong, 528010
Fujian Medical University - Fujian Provincial Cancer Hospital
Fuzhou, Fujian, 350014
First Affiliated Hospital of Gannan Medical University
Ganzhou, Jiangxi, 341001
Cancer Center of Guangzhou Medical University
Guangzhou, Guangdong, 510095
The Sixth Affiliated Hospital Sun Yat-Sen University
Guangzhou, Guangdong, 510655
The First Affiliated Hospital - Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Sir Run Run Shaw Hospital - Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150040
The First Affiliated Hospital of Jinzhou Medical University
Jinzhou, Liaoning, 121011
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
The Second People's Hospital of Neijiang
Neijiang, Sichuan, 641000
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Huashan Hospital Fudan University
Shanghai, Shanghai Municipality, 200040
Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200092
Shanghai East Hospital, Tongji University
Shanghai, Shanghai Municipality, 200120
Cancer Hospital Affiliated to Shantou University Medical College
Shantou, Guangdong, 515041
The First Hospital of China Medical University
Shenyang, Liaoning, 110001
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, 110042
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
Union Hospital Tongji medical college Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430030
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430071
Shaanxi Provincial People's Hospital
Xi'an, Shaanxi, 710068
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361001
Henan Cancer Hospital
Zhengzhou, Henan, 450008
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052
About this study
Official title: A Multicenter, Randomized, Open-label, 2-arm, Phase II Study With a Safety lead-in Phase Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.
Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.
- Conditions
- BRAF V600E, Metastatic Colorectal Cancer
- Being tested
- Encorafenib, Cetuximab, FOLFIRI
- Keywords
- BRAF V600E, Metastatic Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EncorafenibDrug
Also called Braftovi®, PF-07263896, W0090, LGX818
oral hard capsule
CetuximabDrug
Also called Erbitux®, C225
intravenous infusion
FOLFIRIDrug
Also called Folinic acid + Fluorouracil + Irinotecan
Combination of:
irinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Encorafenib and cetuximab | Experimental | Safety Lead-in (SLI) phase:
28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly
Randomized (Phase II) phase:
28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Receives: Drug: Encorafenib; Drug: Cetuximab |
| Irinotecan and cetuximab or FOLFIRI and cetuximab | Experimental | Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles.
Irinotecan and cetuximab:
* irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and
* cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly
OR
FOLFIRI and cetuximab:
* irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks
* Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks
* 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and
* cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Receives: Drug: Encorafenib; Drug: Cetuximab; Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Secondary outcomes (53)
Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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...).
Measured: 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
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.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
Randomized Phase 2: Overall Survival (OS)
OS was defined as time from randomization until date of death due to any cause.
Measured: 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
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.
Measured: 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)
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.
Measured: Day 1 until 30 days after study intervention discontinuation
Randomized Phase 2: Number of Participants With Serious TEAEs
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.
Measured: Day 1 until 30 days after study intervention discontinuation
Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities
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.
Measured: Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
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.
Measured: 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
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.
Measured: 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
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.
Measured: Day 1 until 30 days after last dose of study treatment
Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities
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...).
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Cycle 2 Day 1 until 30 days safety follow-up
Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start14 Sep 2021
- Primary completion19 Dec 2023
- Study completion7 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BRAF V600EStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pierre Fabre Medicament
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Shen Lin, MD, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004350
- Sponsor's protocol ID
- W00090GE202
- Acronym
- NAUTICALCRC
- Status last verified
- Feb 2026
- First submitted
- 30 Apr 2021
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Xicheng W, Yanhong D, Yanqiao Z, Tianshu L, Xianglin Y, Jianwei Y, Tao Z, Aimin Z, Yu L, Li H, Feng Y, Hong Z, Yi B, Isabelle K, Jean-Claude V, Melanie G, Angela G, Jian L, Lin S. A Randomized Trial of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or FOLFIRI/Cetuximab in Chinese Patients With BRAFV600E Mutant Metastatic Colorectal Cancer: The NAUTICAL Study. Cancer Med. 2026 Mar;15(3):e71697. doi: 10.1002/cam4.71697.
PubMed 41852303