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

GIST Clinical Trial

— AVIATOR2020  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04927260
• Other study ID #: AVIATOR2020
• Status: Active, not recruiting
• Start date: March 31, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: December 31, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PDGFRa 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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• GIST
• GIST, Malignant
• PDGFR-Alpha D842V

Intervention

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.

Locations

Country	Name	City	State
France	CHRU Besançon	Besançon
France	Insitut Bergonié	Bordeaux
France	CHU Clermont Ferrand	Clermont-Ferrand
France	Centre Léon Bérard	Lyon
France	Institut de Cancérologie de l'Ouest (ICO)	Nantes
France	CHU Robert Debré	Reims
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Centre Leon Berard	Blueprint Medicines Corporation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	survival of patients treated with Avapritinib in real life according to overall survival.	up to 48 months
Secondary	Progression Free Survival	according to RECIST criteria	after 12, 24 and 36 months
Secondary	Incidence of long-term responders	(>24 months)	up to 48 months
Secondary	Duration of treatment	duration in months	up to 48 months
Secondary	Safety: Nature of AEs	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 48 months
Secondary	Safety : Frequency of AEs	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 48 months
Secondary	Safety : Severity of AEs	AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 48 months
Secondary	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
Secondary	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
Secondary	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