Optimization of the Time and Dosage of Vemurafenib in BRAF Positive Juvenile Patients With Refractory Histiocytosis (BRAVO)

January 12, 2024 updated by: Anna Raciborska
Prospective, interventional, open, randomized, single-center, non-commercial clinical trial to optimize treatment and dosage of vemurafenib in juvenile patients with histiocytosis resistant to conventional therapy and in whom the BRAF gene mutation has been found.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

BRAVO clinical study is part of the POLHISTIO project. The POLHISTIO project is a non-commercial clinical trial aimed at optimizing the diagnosis and treatment of juvenile patients with histiocytosis. The project objectives are defined as follows: 1) to estimate the nature and frequency of mutations in patients with histiocytosis in both tumor tissues and free-circulating DNA; 2) to compare molecular test results with clinical data; 3) to evaluate the diagnostic usefulness of the status of molecular analysis (MRD) as a prognostic factor compared with other recognized factors; 4) in the case of failure of conventional therapy - to modify treatment and to apply targeted treatment, based on molecular status of gene mutation. The project is intended to include patients from all over Poland.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Poland
    • Mazovian
      • Warsaw, Mazovian, Poland, 01-211
        • Recruiting
        • Mother and Child Institute
        • Contact:
        • Principal Investigator:
          • Anna Raciborska

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The presence of mutations in the BRAF gene in tumor tissues and/or in circulating tumor DNA (ctDNA) at any stage of treatment or follow-up.

  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
    3. Third or subsequent reactivation of disease with or without risk organ involvement, or
    4. Reactivation of disease after Vemurafenib therapy has been completed, or
    5. 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 Vemurafenib treatment) according with current legal regulations.
  4. Consent to the use of effective contraception throughout the Vemurafenib 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 Vemurafenib.
  6. Persistent toxicity related to prior therapy, making it impossible to treat with Vemurafenib.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: R1 time of vemurafenib treatment
vemurafenib will be given to 6 months after BRAF negativization
Drug: Vemurafenib
20 mg/kg/day
Other Names:
  • Zelboraf
Experimental: R2 time of vemurafenib treatment
vemurafenib will be given to 12 months after BRAF negativization
Drug: Vemurafenib
20 mg/kg/day
Other Names:
  • Zelboraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
event-free survival
Time Frame: 2 years
Event-free survival (EFS) was defined as the time interval from the date of diagnosis to the date of disease progression, recurrence, second malignancy, death or to date of last follow-up for patients without events.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Molecular relapse (in ct DNA)
Time Frame: 2 years
Molecular relapse was defined as the time interval from the date of BRAF negativization to the date of positive results of BRAF mutation
2 years
Time to negative mutation test results (in ct DNA)
Time Frame: 2 years
Time to negative mutation test results (in ct DNA) was defined as the time interval from the date of positive BRAF mutation to the date of negative results of BRAF mutation
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anna Raciborska

Collaborators

Maria Sklodowska-Curie National Research Institute of Oncology
Łukasiewicz Research Network
Wrocław University of Environmental and Life Sciences

Investigators

  • Principal Investigator: Anna Raciborska, Mother and Child Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2021

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

June 23, 2026

Study Registration Dates

First Submitted

June 21, 2021

First Submitted That Met QC Criteria

June 28, 2021

First Posted (Actual)

June 29, 2021

Study Record Updates

Last Update Posted (Actual)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRAVO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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