Addition of binimetinib after refractory to encorafenib and cetuximab in patients with BRAF V600E-mutant metasta tic colorectal cancer

JRCT ID: jRCTs031210510

Registered date:01/01/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Unresectable, advanced or recurrent colorectal cancer with BRAF V600E mutation
• Date of first enrollment: 24/02/2022
• Target sample size: 30
• Study type: Interventional

Intervention(s)

Encorafenib 300 mg once daily
Binimetinib 45 mg twice daily
Cetuximab 400 mg/m^2 Day 1, 250 mg/m^2 Day 8, 15, 22 (250 mg/m^2 from Cycle 2 later)
These treatments are repeated every 28 days in one cycle.

Outcome(s)

• Primary Outcome: Progression-free survival rate at 12 weeks after first protocol treatment

Secondary Outcome

Progression-free survival (PFS)
Objective response rate (ORR)
Disease control rate (DCR)
Time to treatment failure (TTF)
Overall survival (OS)
Rate of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Unresectable adenocarcinoma of the colon or rectum (excluding appendiceal carcinoma and anal canal carcinoma) was diagnosed by histological examination
2. Wild-type RAS and BRAF V600E mutation in tumor tissue
3. The best overall response (RECIST Guidelines ver 1.1) was CR, PR, SD (>= 4 months), nonCR/nonPD (>= 4 months) for combination therapy including encorafenib and cetuximab
4. PD by imaging or clinical PD was confirmed within 4 weeks after the last dose of encolafenib
5. No history of MEK inhibitor administration
6. Participating in or planning to participate in the GOZILA trial
7. ECOG PS 0 or 1
8. Age on the date of consent >= 20 years old
9.Possible to take drugs orally
10.Applicable starting doses of encorafenib, binimetinib, and cetuximab as defined in this trial
11. Adequate organ function confirmed by laboratory values measured within 14 days before enrollment
12.Written consent obtained from the patient

Exclude criteria

1. Patients have the following serious complications;
a. Active double or more cancer
b. Poorly controlled brain metastasis or leptomeningeal metastasis
c. Active infections
d. Ascites, pleural effusion or pericardial effusion requiring continuous drainage at the date of registration
e. Uncontrolled diabetes mellitus or hypertension
f. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (NYHA Class 3 or 4) within the previous 6 months from enrollment
g. Patients with or at risk of previous or current retinal vein occlusion.
h. Psychosis or psychiatric symptoms that make it difficult to participate in this study
2. The following therapy before first protocol treatment;
a. Extensive surgery within 4 weeks
b. Enterostomy within 2 weeks
c. Any antineoplastic treatment within 2 weeks(Encolafenib, cetuximab, and 5-FU are acceptable)
3. Unrecovered adverse events from prior treatment
4. History of serious allergy to encorafenib or cetuximab
5. Severe lung disease
6. Pregnant, lactating, positive pregnancy test, or unwilling to prevent pregnancy
7. Gilbert syndrome or known UGT1A1*6/*6, UGT1A1*28/*28, UGT1A1*6/*28

Related Information

• Primary Sponsor: Bando Hideaki
• Secondary Sponsor: Yoshino Takayuki
• Source(s) of Monetary Support: ONO PHARMACEUTICAL CO., LTD.