Actively Recruiting

Phase 2
Age: 18Years - 85Years
All Genders
Healthy Volunteers
NCT06229340

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

Led by N.N. Petrov National Medical Research Center of Oncology · Updated on 2024-01-29

20

Participants Needed

1

Research Sites

156 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 85Years
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Able to provide informed consent to participate
  • At least 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Histologically confirmed metastatic stage 4 disease
  • Documented RAS (KRAS, HRAS, NRAS) mutation identified within the last 5 years from tumor tissue
  • Received more than 2 lines of standard anti-tumor drug therapy
  • Disease progression according to RECIST version 1.1 criteria
  • Adequate hematologic and liver function including:
    • Absolute neutrophil count at least 1.5 x 10^9/L
    • Lymphocyte count at least 0.5 x 10^9/L
    • Platelet count at least 100 x 10^9/L without transfusion
    • Hemoglobin at least 90 g/L without transfusion
    • Creatinine clearance at least 40 mL/min
    • Serum albumin at least 25 g/L
    • Serum bilirubin at most 1.5 times normal, or up to 3 times normal for patients with Gilbert's disease or liver metastases
    • AST, ALT, and alkaline phosphatase at most 2.5 times normal
  • For women of childbearing potential: agree to abstain from heterosexual intercourse or use two effective contraception methods during treatment
  • Patients with asymptomatic new or advanced brain metastases eligible if no localized treatment needed by physician
Not Eligible

You will not qualify if you...

  • Older than 85 years
  • Presence of acute or active chronic infections
  • Impaired kidney or liver function or left ventricular ejection fraction below 45%
  • History of acute or chronic hepatitis B or C
  • Allergic reactions to leflunomide, teriflunomide, or similar drugs
  • Uncontrolled diseases such as active infection, symptomatic heart failure, unstable angina, arrhythmias, or mental health/social issues limiting study compliance
  • Pregnant or breastfeeding women
  • History of retinal diseases or current risk factors for retinal problems such as glaucoma or hypercoagulability syndromes
  • Refusal to continue study participation
  • Intolerable toxicity
  • Disease progression requiring change in treatment
  • Non-compliance with study procedures

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

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

Saint Petersburg, Russia

Actively Recruiting

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Research Team

E

Evgeny Imyanitov

CONTACT

L

Liliya Baboshkina

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

CROSSOVER

Primary Purpose

BASIC_SCIENCE

Number of Arms

3

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