French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients

Active, not recruiting

• Conditions: GIST, Malignant; PDGFR-Alpha D842V; GIST
• Interventions: Drug: Patient treated by Avapritinib in real life

• Registration Number: NCT04927260
• Lead Sponsor: Centre Leon Berard

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-31
• Study First Submitted: 2021-06-02
• Study First Submitted QC: 2021-06-09
• Study First Posted: 2021-06-15
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-26
• Primary Completion: 2024-04-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 25

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
COHORTE PROSPECTIF	Patient treated by Avapritinib in real life	-
COHORTE RETROSPECTIF	Patient treated by Avapritinib in real life	-

Primary Outcome Measures

Name	Time	Method
Survival	up to 48 months	survival of patients treated with Avapritinib in real life according to overall survival.

Secondary Outcome Measures

Name	Time	Method
Safety : Frequency of AEs	up to 48 months	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of long-term responders	up to 48 months	(\>24 months)
Duration of treatment	up to 48 months	duration in months
Safety: Nature of AEs	up to 48 months	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Cognitive impairment in real-life according to FACT-Cog	Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36	Functional Assessment of Cancer Therapy - Cognitive Function
Quality of life in real-life according to FACT-G questionnaire	Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36	Functional Assessment of Cancer Therapy - General
Cognitive impairment in real-life according to MoCA questionnaires	Day 1, Day 15, Month 2, Month 3, Month 6, Month 12, Month 18, Month 24, Month 36	Montreal Cognitive Assessment (MoCA)
Progression Free Survival	after 12, 24 and 36 months	according to RECIST criteria
Safety : Severity of AEs	up to 48 months	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Trial Locations

Locations (7)

Centre Léon Bérard; 🇫🇷 Lyon, France

Insitut Bergonié; 🇫🇷 Bordeaux, France

CHU Robert Debré; 🇫🇷 Reims, France

CHRU Besançon; 🇫🇷 Besançon, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

CHU Clermont Ferrand; 🇫🇷 Clermont-Ferrand, France

Institut de Cancérologie de l'Ouest (ICO); 🇫🇷 Nantes, France