Colorectal cancer
Conditions
Interventions
Combination therapy of encorafenib + binimetinib+ cetuximab One cycle is 28 days. Binimetinib: 45 mg, twice daily, oral Encorafenib: 300 mg, once daily, oral Cetuximab: 400 mg/m2 for initial dose
Sponsors
National Cancer Center Hospital Eas
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet all of the inclusion criteria A and B, and do not fall under the any of exclusion criteria will be enrolled as patients for study treatment. At least 8 patients with lesions eligible for biopsy should be enrolled in the primary analysis parts; biopsy of lesions of which measurement in accordance with the RECIST version 1.1 is performed is accepted. Inclusion criteria A 1.Age of 20 years or older on the day of signing informed consent 2.Confirmed diagnosis of advanced (unresectable) or metastatic colorectal cancer (mCRC) by tissue diagnosis 3.Patients who did not respond to or tolerate at least one chemotherapy regimen (including irinotecan or oxaliplatin) containing fluoropyrimidine drugs in the treatment of metastatic CRC, and are thus eligible for second or later line treatment 4.RAS wild-type and BRAF non-V600E mutated CRC. The diagnosis should be based on the results of associated genetic tests, and the record should be available 5.Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 Inclusion criteria B: 1.Measurable lesions in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 2.Patients with the adequate organ functions 3.Adequate cardiac function characterized by the following at screening 1)Left ventricular ejection fraction (LVEF) over 50% as determined by a MUGA scan or ECHO; 2)Mean triplicate QT interval corrected for heart rate using Fridericia's formula (QTcF) value less than 480 msec 4.Women of childbearing potential who are negative in a urine pregnancy test 5.Female patients and male patients must agree to take appropriate precautions to avoid pregnancy from the day of signing informed consent through 90 days after the final administration of investigational drugs.
Exclusion criteria
Exclusion criteria: 1.History of treatment with epidermal growth factor receptor (EGFR) inhibitors including anti-EGFR antibody drugs 2.History of treatment with BRAF inhibitors or MEK inhibitors 3.History of treatment with regorafenib 4.Symptomatic brain metastases or meningeal dissemination 5.Leptomeningeal disease 6.Medical history, current condition, or risk of retinal vein occlusion 7.Inadequately controlled diabetes requiring insulin therapy 8.Acute or chronic pancreatitis 9.Medical history of clinically significant cardiac diseases 10.Gastrointestinal function or gastrointestinal diseases that significantly interfere with absorption, distribution, metabolism, and excretion of the study drugs 11.No history of other malignant tumors within 3 years before the start of study treatment. In cases of lesions corresponding to carcinoma in situ and intramucosal carcinoma judged to be cured by local therapy, non-metastatic prostate cancer not requiring systemic therapy, and other solid cancers that do not require therapy or are not estimated to be adversely affected by the study treatment, patients will not be excluded from the study when the coordinating committee concludes after consultation that there is no effect on the patient's prognosis. 12.Medical history of thromboembolism within 6 months 13.Concurrent neuromuscular disorder that is associated with the potential of elevated CK 14.Previous treatment with any of the following, a.cyclical chemotherapy within a period of 14 days b.bevacizumab, aflibercept, or ramucirumab within 3 weeks c.biologic therapy (except bevacizumab, aflibercept, or ramucirumab), immunotherapy, marketed small molecular compounds, or non marketed investigational anticancer treatments within 4 weeks, or within a period 5fold the halflife (whichever is shorter) d.prior radiotherapy to 30% of bone marrow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed objective response rate by investigators' assessment | — |
Countries
Japan
Contacts
Public ContactDaisuke Kotani
National Cancer Center Hospital East Department of Gastrointestinal Oncology
Outcome results
None listed