This study will evaluate efficacy and safety of hydroxychloroquine combined with methotrexate, capecitabine and bevacizumab versus regorafenib in participants with refractory metastatic colorectal cancer with mutations in KRAS or NRAS genes. The hypotheses of this study are that a combination of hydroxychloroquine, methotrexate, capecitabine, and bevacizumab (compared to regorafenib) prolongs progression-free survival and overall survival, and also increases rates of objective responses and disease control.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Provide written informed consent
Age ≥ 18 years
Histologically confirmed diagnosis of colorectal cancer (CRC) with distant metastases.
Presence of clinically significant cardiovascular disease: severe or unstable ischemic heart disease, history of myocardial infarction, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias.
Stroke and/or transient ischemic attack within 6 months prior to screening;
Uncontrolled hypertension
History of previous malignancies except non-melanoma skin cancers, or in situ cervical or breast cancer unless a complete remission was achieved at least 2 years prior to randomization AND no additional therapy is required during the study period. Patients having hepatic involvement of cancer should be excluded as per investigator assessment.
Sergey Orlov, MD
Lead sponsor
Pavlov First Saint Petersburg State Medical University
Sponsor institution