Actively Recruiting
Encorafenib plus Cetuximab Beyond Progression with FOLFIRI in Patients with BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib plus Cetuximab
Led by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Updated on 2025-02-12
25
Participants Needed
3
Research Sites
25 weeks
Total Duration
On this page
Sponsors
F
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Lead Sponsor
P
Pierre Fabre Pharma GmbH
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the activity of encorafenib plus cetuximab combined with FOLFIRI chemotherapy in patients who have BRAF V600E mutated metastatic colorectal cancer that has progressed after treatment with encorafenib plus cetuximab in the second line. This phase II, single-arm trial aims to understand how this combination treatment works beyond progression in this specific patient group. Participants will receive encorafenib 300 mg orally once daily, cetuximab 500 mg per square meter intravenously every 14 days, and FOLFIRI chemotherapy intravenously every 14 days, which includes irinotecan, folinic acid, and 5-fluorouracil given both as a bolus and continuous infusion. Treatment continues until disease progression, unacceptable side effects, withdrawal of consent, or death. During the study, patients will be monitored for disease progression and response through imaging and clinical assessments. The primary measure is the rate of patients alive and progression-free at 6 months after starting the investigational treatment. Secondary measures include overall survival, duration of response, overall response rate, disease control rate, and adverse events. Participants will be evaluated regularly to track these outcomes and ensure safety throughout the trial period, which runs until June 2026.
CONDITIONS
Brief Title
Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab.
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide written informed consent for study procedures
- Be 18 years of age or older
- Have a confirmed diagnosis of colorectal adenocarcinoma
- Have radiological evidence of metastatic disease
- Have measurable disease based on RECIST 1.1 criteria
- Have a BRAF V600E mutation detected in tumor tissue by local PCR or NGS assay
- Have disease progression while on encorafenib plus cetuximab (EC) in the second line setting
- Have achieved complete response, partial response, or stable disease lasting at least 3 months to prior EC treatment
- Be fit for treatment with FOLFIRI chemotherapy
- Have life expectancy of at least 3 months
- Have an ECOG performance status of 0 or 1
- Have adequate bone marrow function (ANC ≥ 1.5 × 10^9/L, platelets ≥ 100 × 10^9/L, hemoglobin ≥ 9.0 g/dL)
- Have adequate renal function (creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min)
- Have adequate liver function (bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN or ≤5 × ULN with liver metastases)
- Have adequate cardiac function (QTcF ≤ 480 msec)
- Have available treatment-naïve archival tumor tissue sample
- Be able to take oral medications
- Use adequate contraception if of childbearing potential during and 180 days after treatment
- Be willing and able to comply with the protocol
You will not qualify if you...
- Disease progression as best response to prior encorafenib plus cetuximab treatment
- Contraindications to BRAF inhibitor or anti-EGFR therapies
- Contraindications to irinotecan or fluoropyrimidines
- DPYD deficiency
- Life expectancy less than 3 months
- ECOG performance status greater than 1
- Recent serious cardiac events or conditions within 6 months prior to treatment
- Congenital long QT syndrome
- Impaired gastrointestinal function affecting drug absorption
- Uncontrolled blood clotting disorders
- Known Gilbert's syndrome or certain UGT1A1 genotypes
- Active infections requiring systemic therapy
- History of acute or chronic pancreatitis
- Known HIV/AIDS infection
- Positive hepatitis B or C infection at screening
- Symptomatic brain metastases or leptomeningeal disease
- Residual grade >2 toxicity from prior anticancer therapy (except alopecia or neuropathy)
- Current use of contraindicated medications including strong CYP3A4 inhibitors
- Use of St. John's Wort
- Other severe medical or psychiatric conditions that increase risk or interfere with study
- Other malignancies within past 3 years except certain treated skin or noninvasive cancers
- Pregnant or breastfeeding women
- Positive or missing pregnancy test in women of childbearing potential
- Unwillingness to use contraception if sexually active and of childbearing potential
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Until disease progression, unacceptable toxic effects, withdrawal of consent, or death
Participants receive encorafenib orally once daily, cetuximab intravenously every 14 days, and FOLFIRI chemotherapy intravenously every 14 days until disease progression, unacceptable side effects, withdrawal, or death.
Intravenous treatments every 14 days with oral medication daily
Trial Site Locations
Total: 3 locations
1
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Not Yet Recruiting
2
Fondazione Policlinico Universitario Agostino Gemelli, IRCCS
Roma, Italy, 00136
Actively Recruiting
3
Ospedale Cardinale G. Panico
Tricase, Italy, 73039
Actively Recruiting
Research Team
M
Maria Alessandra Calegari
M
Maria Alessandra Calegari
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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