Clinical trial NCT04927260: French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients
Official title: French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients : AVapritinib Real-life observatTORy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: GIST
GIST, Malignant
PDGFR-Alpha D842V
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Blueprint Medicines Corporation
First posted: 2021-06-15
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with GIST harboring a PDGFRa D842V mutation diagnosed from 2010 and treated with Avapritnib or not can be included.

Brief summary: GIST are rare mesenchymal tumors of the gastrointestinal tract characterized by somatic mutations in the gene encoding the KIT (85%) or the PDGFRα (8%) protein. Treatment of localized forms relies on adequate surgery without tumor spillage and sometimes systemic treatment with imatinib according to risk of relapse defined by localization, tumor size and mitotic count, as well as mutational status. More than 40% of cases may recur and metastasize. Advanced and relapsing forms are currently treated with oral tyrosine-kinase inhibitors (TKI) of KIT and PDGFR such as imatinib (standard treatment), sunitinib (2nd line) and regorafenib (3rd line). Nevertheless, imatinib has little or no activity in patients harboring the D842V mutation in the exon 18 of PDGFRα (20% of gastric GIST, 6% of all GIST patients). Consequently, other therapeutic alternatives are needed.

Results from the phase I single-arm NAVIGATOR study show that avapritinib has significant efficacy in GIST patients with PDGFRα D842V mutation (ORR = 86 %). In France, an authorization for temporary use (ATUc) starting on September 21st, 2020 has been granted by the National Agency for Safety of Medicines and Health Products (ANSM). It allows the early availability of avapritinib in France while waiting for Market Authorization Approval (AMM). This ATUc is now being followed by a post-ATU period.

The objective of this real-life registry is to perform a long-term longitudinal follow up of PDGFRA D842V-mutated GIST patients and to collect effectiveness and safety data. It will be implemented in parallel to the post-ATUc period until June 2023.

Moreover, this registry fulfills the HAS's ("Haute Autorité de Santé") request regarding the Establishment of an exhaustive registry of patients with GIST, harboring the D842V / PDGFRA mutation in France. This registry will specifically describe:

* patient characteristics, in particular patient age, of the disease characteristics, previous treatments;
* the clinical course;
* the occurrence of adverse events / effects;
* and the therapeutic strategy (endpoint of treatment or continuation).

Data from the electronic health record (EHR) will be collected. Moreover, as per the ANSM's requirements, quality of life and cognitive function will be investigated using FACT-G, FACT-Cog and MoCA questionnaires.

Undesirable effects will be collected as well. Follow-up is envisioned for a minimum of 2 years.


Eligibility criteria: Inclusion Criteria:

* I1. Adult (≥18 years old), male or female
* I2. Patient with a histologically or cytologically-confirmed diagnosis of unresectable or metastatic GIST harboring the D842V mutation in the PDGFRα gene
* I3. . Diagnosis date later than Jan 1st 2010
* I4. Non opposition to the use of her/his data

Exclusion criteria :

* E1. Patient not meeting all the inclusion criteria

Primary outcomes:
measure: Survival
timeFrame: up to 48 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: after 12, 24 and 36 months
measure: Incidence of long-term responders
timeFrame: up to 48 months
measure: Duration of treatment
timeFrame: up to 48 months
measure: Safety: Nature of AEs
timeFrame: up to 48 months
measure: Safety : Frequency of AEs
timeFrame: up to 48 months
measure: Safety : Severity of AEs
timeFrame: up to 48 months
measure: Cognitive impairment in real-life according to MoCA questionnaires
timeFrame: Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36
measure: Cognitive impairment in real-life according to FACT-Cog
timeFrame: Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36
measure: Quality of life in real-life according to FACT-G questionnaire
timeFrame: Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHRU Besançon
city: Bordeaux
country: France
facility: Insitut Bergonié
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest (ICO)
city: Reims
country: France
facility: CHU Robert Debré
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Leon Berard
name: MEHDI BRAHMI
role: PRINCIPAL_INVESTIGATOR
References: