Optimizing trametinib treatment for juvenile patients with histiocytosis
Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients With Refractory Histiocytosis or After the Failure of Vemurafenib Treatment
PHASE2 · Institute of Mother and Child, Warsaw, Poland · NCT04943224
This study is testing the best way to use trametinib for young patients with histiocytosis who haven't responded to other treatments to see if it can help them better.
Quick facts
| Phase | PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 12 (estimated) |
| Ages | 1 Year to 18 Years |
| Sex | All |
| Sponsor | Institute of Mother and Child, Warsaw, Poland (other) |
| Drugs / interventions | Trametinib |
| Locations | 1 site (Warsaw, Mazovian) |
| Trial ID | NCT04943224 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to optimize the dosage and timing of trametinib for juvenile patients suffering from histiocytosis who do not have the BRAF gene mutation or have failed previous vemurafenib treatment. It is a prospective, interventional, open, randomized, single-center trial that is part of the POLHISTIO project, which focuses on improving the diagnosis and treatment of this condition. The study will evaluate the genetic mutations in patients and their correlation with clinical outcomes, aiming to enhance treatment efficacy based on molecular analysis. The trial is set to include participants from across Poland.
Who should consider this trial
Good fit: Ideal candidates for this study are juvenile patients with histiocytosis who lack BRAF mutations or have not responded to vemurafenib.
Not a fit: Patients with BRAF mutations or those who have not undergone prior conventional therapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a more effective treatment option for juvenile patients with histiocytosis, potentially improving their prognosis.
How similar studies have performed: While this approach is novel in the context of trametinib for this specific patient population, similar studies have shown promise in optimizing targeted therapies based on genetic profiles.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Lack of mutations in the BRAF gene in tumor tissues and/or circulating tumor DNA (ctDNA) at any stage of treatment or follow-up, or failure of Vemurafenib treatment in BRAF positive patients. 2. Failure of the treatment (at least one of below needs to apply in order for this requirement to be satisfied): 1. Progression on the I and/or II line treatment, including at least one risk organ; prior treatment should include a minimum of 6 weeks of weekly Vinblastine with a minimum of 28 days prednisolone or minimum 2 cycles of Cytosine Arabinoside in 4-day cycles and/or Cladribine in 5-day cycles as a 2nd line treatment, minimum 2 cycles, or other second-line treatment or 2. Disease reactivation after an initial response to treatment with Vimblastine and prednisolone as the first line and/or no response to second line treatment using one of two drugs: Cytosine Arabinoside in 4- day cycles and/or Cladribine in 5-day cycles, minimum 2 cycles, or other I/ II line treatment or occurrence of involvement of at least one risk organ or d. Progression during Vemurafenib therapy, or e. Reactivation of disease after Vemurafenib therapy has been completed, or f. The appearance of signs of neurodegenerative disorder (ND) in MRI of the central nervous system (CNS). 3. Signing of informed consent for trial participation (including for Trametinib treatment) according with current legal regulations. 4. Consent to the use of effective contraception throughout the Trametinib administration period and a minimum of 1 year after discontinuation in patients at puberty and sexual maturity. 5. Participation in HISTIOGEN trial. Exclusion Criteria: 1. Lack of inclusion criteria. 2. Pregnancy and breastfeeding . 3. Hypersensitivity to the study drug or any of its ingredients. 4. Iritis, uveitis, obstruction of the retinal veins. 5. Simultaneous treatment with other drugs which might interact with Trametinib. 6. Persistent toxicity related to prior therapy, making it impossible to treat with Trametinib. 7. Diagnosis of other malignancies before study inclusion. 8. Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the trial.
Where this trial is running
Warsaw, Mazovian
- Mother and Child Institute — Warsaw, Mazovian, Poland (RECRUITING)
Study contacts
- Principal investigator: Anna Raciborska — Mother and Child Institute
- Study coordinator: Katarzyna Maleszewska
- Email: klinika.onkologii@imid.med.pl
- Phone: +48 22 32 77 205
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Histiocytosis, Langerhans cell histiocytosis, histiocytosis, trametinib, paediatric patients