Actively Recruiting
Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer
Led by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) · Updated on 2024-10-21
70
Participants Needed
1
Research Sites
258 weeks
Total Duration
On this page
Sponsors
S
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Lead Sponsor
M
Merck, S.L., Spain
Collaborating Sponsor
AI-Summary
What this Trial Is About
As a result of the little benefit obtained from standard treatments and the poor prognosis of these patients, the BRAF-V600E mutant MSS aCRC represents an unmet medical need requiring clinical research. The combination of encorafenib, cetuximab and binimetinib as second- or third-line treatment for mCRC resulted in significantly better outcomes than standard therapy in a phase 3 clinical trial, which also revealed treatment safety and tolerability to be acceptable. Compared to the control group (cetuximab and irinotecan or cetuximab and FOLFIRI), the triplet therapy cohort showed higher median overall survival (9.3 vs. 5.9 months) and response rates (26.8% vs. 1.8%). Grade 3 adverse events occurred in 65.8% and 64.2% of patients for triple-therapy and control groups, respectively. Based on these results, the investigators speculated that the combination of encorafenib, cetuximab and binimetinib could be used as induction therapy to improve treatment outcomes in BRAF-V600E-mutated MSS aCRC locally advanced initially unresectable but potentially resectable; initially resectable or initially unresectable but potentially resectable oligometastatic disease; and in patients with stage II-IV who have relapsed after chemotherapy (neo and/or adjuvant) or surgery, if the shorter time after resection or from treatment end to relapse is longer than 6 months.
CONDITIONS
Official Title
Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female participants aged 18 years or older at the time of consent
- Able to provide signed informed consent or assent
- Willing and able to comply with study visits, treatment plans, tests, and procedures
- Histologically or cytologically confirmed colorectal adenocarcinoma
- Presence of BRAF V600E mutation confirmed by standard of care before screening
- Microsatellite stable (MSS) or mismatch-repair proficient disease confirmed by local PCR or immunohistochemistry
- Have locally advanced colorectal cancer initially unresectable but potentially resectable or oligometastatic colorectal cancer that is initially resectable or potentially resectable
- Stage II-IV colorectal cancer that relapsed more than 6 months after surgery or chemotherapy, with disease initially or potentially resectable
- ECOG performance status of 0 or 1
- Measurable or evaluable disease per RECIST v1.1
- Adequate bone marrow function with ANC ≥1.5 × 10^9/L, platelets ≥100 × 10^9/L, hemoglobin ≥9.0 g/dL
- Adequate liver function with total bilirubin ≤1.5 × ULN (with exceptions), ALT and AST ≤2.5 × ULN or ≤5 × ULN if liver metastases present
- Adequate kidney function with creatinine clearance ≥50 mL/min by standard methods
- Able to swallow, retain, and absorb oral medications
You will not qualify if you...
- Any medical or psychiatric condition including recent or current suicidal ideation or lab abnormalities increasing study risk or judged inappropriate by investigator
- Presence of leptomeningeal disease or brain metastases
- History of chronic inflammatory bowel disease requiring treatment within 12 months before study
- Known RAS-mutant colorectal adenocarcinoma
- Impaired gastrointestinal function or disease affecting absorption or recent bowel function changes indicating obstruction
- Significant cardiovascular disease including recent myocardial infarction or acute coronary syndromes within 6 months, heart failure (NYHA grade ≥2), significant arrhythmias, or thromboembolic/cerebrovascular events within 12 weeks
- QTcF interval ≥480 ms or history of prolonged QT syndrome
- Congenital long QT syndrome
- Active non-infectious pneumonitis
- Active and uncontrolled infections including certain viral infections within 2 weeks before treatment
- HIV positive without stable antiretroviral therapy and adequate immune status
- Active hepatitis B or C infection as defined by specific viral markers
- Other malignancies within 3 years except certain low-risk treated cancers
- Residual toxicity grade ≥2 from previous cancer therapy except alopecia or neuropathy
- Prior treatment with selective BRAF or MEK inhibitors
- Use of medications affecting CYP3A4/5 within 1 week before treatment
- Major surgery or radiation therapy within 4 weeks before study treatment
- Prior systemic anticancer therapy for colorectal cancer except allowed adjuvant/neoadjuvant treatments with relapse beyond 6 months
- Previous first-line treatment for metastatic colorectal cancer with unresectable disease
- Use of investigational drugs within 30 days before first dose
- Known contraindications or hypersensitivity to cetuximab or study drug components
- Pregnant or breastfeeding
- Childbearing age participants not agreeing to contraception or abstinence during and 6 months after treatment
- Full dose radiotherapy less than 28 days before treatment start; short course radiotherapy allowed
- Patients with ulcerative keratitis
AI-Screening
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Trial Site Locations
Total: 1 location
1
Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)
Madrid, Spain, 28046
Actively Recruiting
Research Team
E
Esther Mahillo, phD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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