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

A Randomized Trial To Compare Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Versus Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes

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 (NCT06949982) is a Phase 2 interventional studying Metastatic Colorectal Cancer (mCRC) and Colorectal Neoplasms, sponsored by Sergey Orlov, MD. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Metastatic Colorectal Cancer (mCRC) and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 60 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Metastatic Colorectal Cancer (mCRC) subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 - Provide written willing to sign a consent form - Age ≥ 18 years - diagnosed by tissue sample (biopsy-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. Who Should NOT Join This Trial: - 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 cancer that has spread to the brain 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

COMBINATION_PRODUCT

experimental group x-MAP

hydroxychloroquine 200 mg TID PO+ methotrexate 2.5 mg BID twice a week PO+ capecitabine 1000 mg/m2 PO BID for 14 days+ bevacizumab 7.5 mg/m2 IV on day 1, every 3 weeks.

DRUG

Regorafenib (BAY 73-4506)

Regorafenib 160 mg PO daily on days 1-21, every 28 days OR 1st cycle: Regorafenib 80 mg PO daily on days 1-7, followed by 120 mg PO daily on days 8-14, followed by 160 mg PO daily on days 15-21, every 28 days, 2nd and subsequent cycles: Regorafenib 160 mg PO daily on days 1-21, every 28 days

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

First Pavlov State Medical University

Saint Petersburg, Sankt-Peterburg, Russia

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06949982), the sponsor (Sergey Orlov, MD), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06949982 clinical trial studying?

Who can participate in NCT06949982?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06949982?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06949982. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06949982. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.