French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients (AVIATOR2020)

French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients : AVapritinib Real-life observatTORy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: GIST, Malignant; GIST; PDGFR-Alpha D842V
• Intervention / Treatment: Drug: Patient treated by Avapritinib in real life

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • CHRU Besançon
  • Bordeaux, France
    • Insitut Bergonié
  • Clermont-Ferrand, France
    • CHU Clermont Ferrand
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Nantes, France
    • Institut de cancerologie de l'ouest (ICO)
  • Reims, France
    • CHU Robert Debré
  • Villejuif, France
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COHORTE PROSPECTIF	Drug: Patient treated by Avapritinib in real life; The patients included are treated with Avapritinib as part of their care. There is no change in treatment associated with this study. Patients must regularly complete various questionnaires: FACT-G, FACT-COG, and a neuropsychiatrist or a trained physician will give them the MoCA.
COHORTE RETROSPECTIF	Drug: Patient treated by Avapritinib in real life; The patients included are treated with Avapritinib as part of their care. There is no change in treatment associated with this study. Patients must regularly complete various questionnaires: FACT-G, FACT-COG, and a neuropsychiatrist or a trained physician will give them the MoCA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	survival of patients treated with Avapritinib in real life according to overall survival.	up to 48 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Collaborators: Blueprint Medicines Corporation
• Investigators: Principal Investigator: MEHDI BRAHMI, Centre Léon Bérard

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 9, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: AVIATOR2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No