histiocytic cell proliferation MedDRA version: 21.1 Level: PT Classification code 10069698 Term: Langerhans' cell histiocytosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10078782 Term: Langerhans cell sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060801 Term: Erdheim-Chester
Conditions
Interventions
Trade Name: ZELBORAF
Product Name: ZELBORAF
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: VEMURAFENIB
CAS Number: 918504-65-1
Current Sponsor code: wemurafenib
Other descriptive name: V
Sponsors
Institute of Mother and Child
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.The presence of mutations in the BRAF gene in tumor tissues and/or in 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): a. 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 b. 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 c. Third or subsequent reactivation of disease with or without risk organ involvement, or d. Reactivation of disease after Vemurafenib therapy has been completed, or e. The appearance of signs of neurodegenerative disorder (ND) in MRI of the 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. Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Optimalization of the time and dosage of Vemurafenib in BRAF positive juvenile patients with refractory histiocytosis.;Secondary Objective: 1. To evaluate the optimal Vemurafenib treatment duration in BRAF positive juvenile patients with refractory histiocytosis. 2. To determine optimal dosing schedule of the investigated substance in patient below 18 y.o. by monitoring of dose dependent pharmacokinetic parameters and pharmacodynamic effects. 3. To evaluate the safety of Vemurafenib treatment in BRAF positive juvenile patients with refractory histiocytosis. 4. To evaluate pharmacokinetic parameters Cmaxs, Cmins, Css, time to achieve stationary concentration in serum 5. To evaluate the clinical response to Vemurafenib treatment in relation to pharmacokinetics/serum drug concentration. 6. To evaluate organ toxicity of Vemurafenib treatment in relation to pharmacokinetics/serum drug concentration. 7. To evaluate the diagnostic usefulness of the status of molecular analysis of the BRAF mutation in free-circulating DNA as a prognostic factor compared with other recognized factors. ;Primary end point(s): EFS – (event-free survival). Assessment of the safety of vemurafenib treatment by AE analysis including adverse events of a special interest. Assessment of the safety of vemurafenib treatment by vital signs, laboratory tests, echocardiography and ECG findings analysis. To determine dose of the investigated substance in patient below 18 y.o. that provides exposition to the drug similar to exposition recommended in adults.;Timepoint(s) of evaluation of this end point: Interim analyzes were planned after the enrollment of 10 patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS (Progression-Free Survival), • OS (Overall Survival), • ORR (Overall Response Rate), • Reactivation rate after 2 years, • Molecular relapse, • Time to negative mutation test results (in ctDNA), • Maximum concentration in serum in stationary state Cmaxs. • Minimal concentration in serum in stationary state Cmins. • Sporadic concentration in serum in stationary state Css. • Exposition to the drug Ctau. • Time to achieve stationary drug concentration in serum.;Timepoint(s) of evaluation of this end point: Interim analyzes were planned after the enrollment of 10 patients. | — |
Countries
Poland
Contacts
Public ContactDepart. of Oncology and Surgical O
Institute of Mother and Child
Outcome results
None listed