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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)

This study is currently recruiting participants.
See Contacts and Locations
Verified October 2016 by Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere
ClinicalTrials.gov Identifier:
NCT02089724
First received: March 15, 2014
Last updated: October 27, 2016
Last verified: October 2016
  Purpose

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.


Condition
Erdheim-Chester Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease

Resource links provided by NLM:


Further study details as provided by Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: March 2014
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
vemurafenib/other BRAF inhibitors

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02089724

Contacts
Contact: Julien Haroche, MD, PhD +33 1 42 17 80 37 julien.haroche@psl.aphp.fr
Contact: Fleur Cohen Aubart, PD, PhD +33 1 42 17 82 42 fleur.cohen@psl.aphp.fr

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eli L. Diamond, MD, PhD       diamonel@mskcc.org   
Principal Investigator: Eli L. Diamond, MD, PhD         
Sub-Investigator: Omar Abdel-Wahab, MD         
France
AP-HP, Groupe Hospitalier Pitié-Salpêtrière Recruiting
Paris, France, 75013
Contact: Julien Haroche, MD, PhD    +33 1 42 17 80 37    julien.haroche@psl.aphp.fr   
Contact: Fleur Cohen Aubart, MD, PhD    +33 1 42 17 82 42    fleur.cohen@psl.aphp.fr   
Principal Investigator: Julien Haroche, MD, PhD         
Sub-Investigator: Fleur Cohen Aubart, MD, PhD         
Sub-Investigator: Zahir Amoura, MD, MSc         
Sponsors and Collaborators
Groupe Hospitalier Pitie-Salpetriere
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