Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations

Q: Who can participate in NCT06229340?

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.

Q: How do I contact the trial site for NCT06229340?

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.

Q: 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.

Q: 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.

New Therapeutic Approaches for Tumors With RAS Gene Mutations

Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations (NCT06229340) is a Phase 2 interventional studying RAS Mutation and Ras (Kras or Nras) Gene Mutation, sponsored by N.N. Petrov National Medical Research Center of Oncology. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

There is a huge variety of nucleotide substitutions that activate RAS. The search for new "universal" drugs for the RAS pathway that either interfere with RAS upregulation upstream in the signaling pathway or offset the consequences of RAS activation is important for improving therapeutic outcomes for patients with refractory malignancies. The use of leflunomide or the combination of MEK inhibitor + hydroxychloroquine ± bevacizumab is promising for patients with mutations in RAS cascade genes who have failed all existing treatment standards.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against RAS Mutation 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.

With a target enrollment of 20 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Patient is able to provide willing to sign a consent form and sign approved consent forms to participate in the study. 2. Patient age is at least 18 years old. 3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2. 4. diagnosed by tissue sample (biopsy-confirmed) metastatic metastatic disease stage 4. 5. Must have documented RAS (KRAS, HRAS, NRAS) mutation identified within the last 5 years by a local test on tumor tissue. 6. More than 2 lines of standard drug antitumor therapy in the anamnesis. 7. Must have disease progression as defined by RECIST version 1.1 criteria 8. Appropriate hematologic and liver function: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/μL) - Lymphocyte count ≥ 0.5 x 109/L (500/μL) - Platelet count ≥ 100 x 109/L (100,000/μL) without transfusion - blood count (hemoglobin) at least 90 g/L without transfusion. - kidney function (creatinine clearance) at least 40 mL/min - Serum albumin ≥ 25 g/L (2.5 g/dL) - Serum bilirubin ≤ 1.5 x HGH, with the following exception: - Patients with known Gilbert's disease or liver metastases: serum bilirubin level ≤ 3 x IUH - AST, ALT, and alkaline phosphate ≤ 2.5 x HGN; 10\. For women of childbearing potential: consent to abstinence (abstain from heterosexual intercourse) or use at least two forms of effective contraception with an ineffectiveness rate \< 1% per year during treatment. 11\. Patients with asymptomatic new or advanced brain metastases (active brain metastases) are eligible to participate if the treating physician determines that localized treatment is not required. Who Should NOT Join This Trial: 1. Age over 85 years. 2. Рresence of acute or active chronic infections. 3. Impaired renal and hepatic function; - left ventricular ejection fraction (LVEF) \< 45% 4. Known history of acute or chronic hepatitis B or C due to known potential hepatotoxicity of leflunomide. ...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: 1. Patient is able to provide informed consent and sign approved consent forms to participate in the study. 2. Patient age is at least 18 years old. 3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2. 4. Histologically confirmed metastatic metastatic disease stage 4. 5. Must have documented RAS (KRAS, HRAS, NRAS) mutation identified within the last 5 years by a local test on tumor tissue. 6. More than 2 lines of standard drug antitumor therapy in the anamnesis. 7. Must have disease progression as defined by RECIST version 1.1 criteria 8. Appropriate hematologic and liver function: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/μL) * Lymphocyte count ≥ 0.5 x 109/L (500/μL) * Platelet count ≥ 100 x 109/L (100,000/μL) without transfusion * Hemoglobin ≥ 90 g/L without transfusion. * Creatinine clearance ≥ 40 mL/min * Serum albumin ≥ 25 g/L (2.5 g/dL) * Serum bilirubin ≤ 1.5 x HGH, with the following exception: * Patients with known Gilbert's disease or liver metastases: serum bilirubin level ≤ 3 x IUH * AST, ALT, and alkaline phosphate ≤ 2.5 x HGN; 10\. For women of childbearing potential: consent to abstinence (abstain from heterosexual intercourse) or use at least two forms of effective contraception with an ineffectiveness rate \< 1% per year during treatment. 11\. Patients with asymptomatic new or advanced brain metastases (active brain metastases) are eligible to participate if the treating physician determines that localized treatment is not required. Exclusion Criteria: 1. Age over 85 years. 2. Рresence of acute or active chronic infections. 3. Impaired renal and hepatic function; - left ventricular ejection fraction (LVEF) \< 45% 4. Known history of acute or chronic hepatitis B or C due to known potential hepatotoxicity of leflunomide. 5. History of allergic reactions associated with compounds similar in chemical or biological composition to leflunomide or teriflunomide or other drugs in the combination. 6. Uncontrolled intercurrent disease, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, or mental illness/social situations that limit study compliance. 7. Patients should not be pregnant or breastfeeding due to the potential for teratogenic effects and side effects of planned chemotherapeutic regimens. 8. History of retinal disease (retinal tear, exudate, hemorrhage) or retinal vein occlusion, central serous retinopathy or retinal pigment epithelium detachment, or current risk factors for ROS (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes). Exit criteria: 1. Refusal to continue participation in the study. 2. Intolerable toxicity. 3. Progression according to RECIST 1.1 and IRECIST criteria or clinically significant (in the opinion of the physician) progression requiring a change in anticancer treatment. 4. Non-compliance with IND procedures.

Treatments Being Tested

DRUG

Leflunomide

100 mg daily for 3 days at the loading dose, then 20 mg daily at the standard dose.

DRUG

The combination of MEK inhibitor + hydroxychloroquine( plaquenil) ± bevacizumab

Use of one of the possible MEK-inhibitor options: Trametinib 2 mg once daily orally; Cobimetinib 60 mg on days 1-21, break 7 days, cycle 28 days orally; Binimetinib 45 mg 2 times a day daily orally. + Hydroxychloroquine 600 mg 2 times a day daily orally. ± Bevacizumab 7.5 mg/m² every 3 weeks intravenously.

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.

Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation

Saint Petersburg, Russia

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06229340), the sponsor (N.N. Petrov National Medical Research Center of Oncology), 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 NCT06229340 clinical trial studying?

Who can participate in NCT06229340?

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 NCT06229340?

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 NCT06229340. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06229340. 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.