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

Sponsor
N.N. Petrov National Medical Research Center of Oncology
Study ID
NCT06229340
Phase
PHASE2
Status
Recruiting
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Conditions

  • Colorectal Cancer Recurrent
  • Lung Cancer
  • Melanoma
  • Pancreas Cancer
  • RAS Mutation
  • Ras (Kras or Nras) Gene Mutation
  • Refractory Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - 85 Years
Healthy Volunteers
Accepted

Interventions

  • Leflunomide — DRUG
    100 mg daily for 3 days at the loading dose, then 20 mg daily at the standard dose.
  • The combination of MEK inhibitor + hydroxychloroquine( plaquenil) ± bevacizumab — DRUG
    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.

Study Details

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.

Key Dates

First listed
Jan 29, 2024
Start date
Oct 3, 2023
Status verified
Jan 2024
Primary completion
Oct 1, 2026
Completion
Oct 1, 2026

Study Design

Enrollment
20 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Group 1
    Leflunomide
  • Experimental: Group 2
    Combination of MEK Inhibitor and Hydroxychloroquine ( Plaquenil)
  • No Intervention: historical control group
    standard therapy

Primary Outcome Measure

Objective response rate [ Time Frame: at the end of 2 cycles of treatment (each cycle is 28 days) ]

Central Contacts

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