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Trial record 1 of 1 for:    NCT02089724
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Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease (LOVE)

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ClinicalTrials.gov Identifier: NCT02089724
Recruitment Status : Unknown
Verified October 2016 by Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere.
Recruitment status was:  Recruiting
First Posted : March 18, 2014
Last Update Posted : October 28, 2016
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere

Tracking Information
First Submitted Date March 15, 2014
First Posted Date March 18, 2014
Last Update Posted Date October 28, 2016
Study Start Date March 2014
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 17, 2014)
PET scan response [ Time Frame: 6 months (M6) ]
Modification of SUVmax between M0 and M6 will be used as the main evaluation criteria for each lesion. As assessed by PERCIST criteria, patients will be classified as complete metabolic responders (CMR; complete resolution of pathologic 18F-FDG uptake), partial metabolic responders (PMR; reduction of a minimum of 30% in activity of target lesions), stable metabolic disease (SMD; not CMR, PMR, or progressive metabolic disease (PMD; increase of a minimum of 30% in activity of target lesions or presentation of a new lesion). In contrast to the PERCIST suggestions, tumor SUVmax rather than peak SUV will be measured. Target lesion will be defined by the most active lesion on FDG-PET/CT study before treatment and, for each patient, one or two secondary target lesions among the most active lesions will also be studied. Side-by-side image review and analysis will be performed to ascertain that the SUVmax is derived from the same lesions on baseline and follow-up scans
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02089724 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: March 17, 2014)
  • Specific organ assessment (cardiac, retroperitoneal, neurological) [ Time Frame: Months 6 and Months 12 ]
  • PET scan [ Time Frame: Months 12 ]
  • CRp value (mg/liter) [ Time Frame: Months 6 and Months 12 ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
Official Title Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
Brief Summary

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Diagnosis of ECD is based on clinical symptoms, imaging and histology with infiltration of tissues by foamy CD68 positive CD1a negative histiocytes.

Because half of the ECD patients carry a BRAFV600E mutation, we recently proposed vemurafenib, an inhibitor of mutant BRAF, as a possible targeted therapy. We have treated more than10 patients with refractory ECD with life-threatening manifestations associated with the BRAFV600E mutation and observed a short and long term efficacy.

However, vemurafenib may have several side effects and long term administration of this drug has not been evaluated. In other diseases such as melanoma, duration of administration is usually shorter, due to bad prognosis of the disease and progression despite treatment.

As in long-term follow-up, ECD patients with vemurafenib seem to have a stable disease, we want to evaluate the possibility of treatment interruption as this is what we do in our current practice. Other BRAF inhibitors, such as dabrafenib, have recently been proposed for treating BRAF mutated histiocytoses. Other BRAF inhibitor interruption treatment should also be prospectively evaluated.

Detailed Description

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Diagnosis of ECD is based on clinical symptoms, imaging and histology with infiltration of tissues by foamy CD68 positive+ CD1a negative histiocytes. The clinical course mainly depends on the extent and distribution of the disease, and ranges from asymptomatic bone lesions to life-threatening manifestations. The overall mortality remains high (22% of the 100 ECD patients seen at our institution in August 2013).

Due to the rare nature of the disease (500 cases worldwide have been reported since 1930) no prospective therapeutic trial has been performed. Interferon alpha (IFN alpha), in its standard or pegylated forms, is the first line therapy for ECD. However, long-term IFN alpha treatment can lead to severe side effects. Moreover, some patients with CNS and/or cardiovascular infiltrations, the two lethal organ involvement, develop secondary resistance to high doses of IFN alpha. For refractory patients, anakinra, cladribine, tyrosine kinase inhibitors, or infliximab have been proposed as second line treatments. The optimal second line therapeutic strategy remains however to be defined, mostly because these treatments have been evaluated in only small numbers of patients.

Because half of the ECD patients carry a BRAFV600E mutation, we recently proposed vemurafenib, an inhibitor of mutant BRAF, as a possible targeted therapy. We have treated 10 patients with refractory ECD with life-threatening manifestations associated with the BRAFV600E mutation and observed a short and long term efficacy (median follow-up 9 months).

However, vemurafenib may have several side effects and long term administration of this drug has not been evaluated. In other diseases such as melanoma, duration of administration is usually shorter, due to bad prognosis of the disease and progression despite treatment.

As in long-term follow-up, ECD patients with vemurafenib seem to have a stable disease, we want to evaluate the possibility of treatment interruption as this is what we do in our current practice. Other BRAF inhibitors, such as dabrafenib, have recently been proposed for treating BRAF mutated histiocytoses.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Study population description is patients with Erdheim-Chester disease who have been treated with vemurafenib or other BRAF inhibitor
Condition Erdheim-Chester Disease
Intervention Not Provided
Study Groups/Cohorts vemurafenib/other BRAF inhibitors
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: March 17, 2014)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date April 2019
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age superior or equal to 18 years
  • Clinical and radiological presentation concordant with ECD
  • Presence of histological proof of ECD
  • Treatment with vemurafenib or other BRAF inhibitor
  • Agreement to participate

Exclusion Criteria:

  • Pregnancy
  • Patients who exceed the safe weight limit of the PET/CT bed (220 kg) or who cannot fit through the PET/CT bore (diameter 70 cm).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02089724
Other Study ID Numbers medint001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere
Study Sponsor Groupe Hospitalier Pitie-Salpetriere
Collaborators Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Julien Haroche, MD, PhD Groupe Hospitalier Pitié-Salpêtrière
Study Director: Fleur Cohen Aubart, MD, PhD Groupe Hospitalier Pitié-Salpêtrière
Study Chair: Eli L. Diamond, MD, PhD Memorial Sloan Kettering Cancer Center
PRS Account Groupe Hospitalier Pitie-Salpetriere
Verification Date October 2016