Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Vs. Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes

Inclusion Criteria:

* 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 mutations in the KRAS or NRAS gene.
* Participants must have previously treated for metastatic colorectal cancer and experienced disease progression during receiving at least 2 lines of systemic chemotherapy in combination with antiangiogenic agents.
* Patient has previously received oxaliplatin- and irinotecan-containing regimens and developed resistance to these chemotherapeutic agents.

Exclusion Criteria:

* 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.
* Patients with CNS metastases are eligible only if the metastases are adequately treated.
* Absolute neutrophil count (ANC) \<1.5×109/L, platelet count \<100×109/L, or hemoglobin \<9.0 g/dL.
* Serum total bilirubin \>1.5 × the upper limit of normal (ULN). Participants with Gilbert syndrome, bilirubin \<2 X ULN, and normal AST/ALT are eligible;
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × ULN;
* Serum creatinine \>1.5 × ULN.
* History of a thromboembolic event
* Presence of any allergic reactions to components of the study drugs
* Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes.
* Any anti-cancer systemic therapy, radiation therapy
* Women who are pregnant or lactating;
* Presence of unresolved adverse events of grade 2 or higher toxicity, according to CTCAE v5.0 criteria, from prior therapy (except for alopecia or neurotoxicity grade≤2).
* Any other serious or uncontrolled medical disorder, active infection, physical examination finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a patient's ability to comply with the study requirements, substantially increase risk to the patient, or impact the interpretability of study results.