Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients

Plain-language summary

This study aims to optimize the timing and dose of the drug Trametinib in children with refractory histiocytosis who do not carry a BRAF mutation (or whose Vemurafenib treatment has failed). Patients without a BRAF mutation in tumor tissue or ctDNA whose prior treatments have failed, and who are enrolled in the HISTIOGEN trial, could take part. It is a Phase 2 study and is still recruiting participants.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 2

Status

Recruiting

Sponsor

Anna Raciborska

Intervention

Trametinib

Start date

4/1/2021

Estimated completion

6/30/2027

Countries

Poland

Related genes

Locations

• Warsaw, Poland

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.