Pre-treated BRAFV600E metastatic colorectal adenocarcinoma.
Conditions
Interventions
Trade Name: Erbitux
Pharmaceutical Form: Solution for infusion
Trade Name: Braftovi
Pharmaceutical Form: Capsule, hard
Sponsors
Camilla Qvortrup
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Histologically verified CRC, adenocarcinoma pMMR or dMMR. 3. Non-resectable and/or metastatic disease. 4. Measurable and/or evaluable non-measurable disease. 5. Presence of BRAFV600E in tumor tissue by a local laboratory using a PCR or NGS-based assay. 6. No known activating RAS mutations according to local assessments. 7. Patients eligible to receive cetuximab. 9. Performance status (WHO) of 0-1. 10. The patient must have progressed on prior systemic treatment for colorectal cancer. In case of dMMR the patient must have progressed on immumotherapy, unles declared unsuitable for treatment with immunotherapy. 11. Adequate hematological function defined as neutrophils ? 1.5 x 109/l and platelets = 100 x 109/l. 12. Adequate renal function characterized by serum creatinine = 1.5 × upper limit of normal (ULN) or calculated by Cockroft-Gault formula or directly measured creatinine clearance = 50 mL/min at screening. 13. Adequate organ function: bilirubin = 1.5 x UNL (upper normal limit), alanine aminotransferase (ALAT) and/or aspartate aminotransferase. (ASAT) = 2.5 × ULN, or = 5 × ULN in presence of liver metastases. 14. Ability to take oral medications. 15. QT interval corrected for heart rate using Fridericia's formula (QTcF) value =480 msec. 16. Woman of childbearing potential must have been tested negative in a serum pregnancy test within 5 days prior to study drug initiation. 17. Male and female patients who have the potential to reproduce must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) during the study and for 6 months after the discontinuation of study medication. 18. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any RAF inhibitor, MEK inhibitor og EGRF inhibitors 2. Untreated/symptomatic brain metastasis (treated brain metastasis must be stable for 4 weeks or more). 3. Known leptomeningeal disease. 4. Use of any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4/5 = 1 week prior to the start of study treatment. 5. Known history of acute or chronic pancreatitis. 6. History of chronic inflammatory bowel disease or Crohn’s disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) = 12 months prior to study drug initiation. 7. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: 7.1. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or stenting) = 6 months prior to start of study treatment; 7.2. Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality = 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia. 7.3. Uncontrolled hypertension defined as persistent systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg despite current therapy. 8. Impaired hepatic function, defined as Child-Pugh class B or C. 9. Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib or (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption). 10. Therapy for other malignancy within 2 years. 11. History of thromboembolic or cerebrovascular events = 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, or clinically significant pulmonary embolism 12. Treatment with any of the following: 12.1. Cyclical chemotherapy within a period of time that was shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment 12.2. Biologic therapy (e.g., antibodies) except bevacizumab or aflibercept, continuous or intermittent small molecule therapeutics, or any other investigational agents within a period of time that is = 5 half-lives (t1/2) or = 4 weeks (whichever is shorter) prior to starting study treatment 12.3. Bevacizumab or aflibercept therapy = 3 weeks prior to starting study treatment. 13. Radiation therapy that included > 30% of the bone marrow within the last 4 weeks. 14. Residual CTCAE = Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy. 15. Known history of HIV infection. 16. Active hepatitis B or hepatitis C infection. 17. Known contraindication (e.g. hypersensitivity to the active substances of the treatment or any of their excipients) to receive cetuximab at the planned doses; refer to the most recent cetuximab, SPC or local label as applicable. 18. Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to evaluate the efficacy and tolerability of cetuximab every second week together with encorafenib in patients with pre-treated, metastatic BRAF-mutated colorectal adenocarcinoma. Primary objective is 2 months Progression Free Survival (PFS) rate.;Secondary Objective: Secondary objectives include Overall Survival (OS), PFS, Response Rate (RR), Toxicity and Correlation between tumor makers and makers of resistance and outcome;Primary end point(s): 2 months PFS rate;Timepoint(s) of evaluation of this end point: 6 months after end of trial (last visit last patient) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS PFS RR Toxicity Correlation tumor markers and outcome Correlation between markers of resistance and outcome;Timepoint(s) of evaluation of this end point: 6 months after end of trial (last visit last patient) | — |
Countries
Denmark
Contacts
Public ContactDepartmenf of Oncology
Camilla Qvortrup
Outcome results
None listed