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

NCT04927260 | Unknown FDA Drug

• 1 other identifier: AVIATOR2020
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 7

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.

Conditions

GIST; GIST, Malignant; PDGFR-Alpha D842V

Outcome Measures

Primary Outcomes (1)

• Survival

  survival of patients treated with Avapritinib in real life according to overall survival.

  up to 48 months

Secondary Outcomes (9)

• Progression Free Survival

  after 12, 24 and 36 months

• Incidence of long-term responders

  up to 48 months

• Duration of treatment

  up to 48 months

• Safety: Nature of AEs

  up to 48 months

• Safety : Frequency of AEs

  up to 48 months

Study Arms (2)

COHORTE PROSPECTIF

Drug: Patient treated by Avapritinib in real life

COHORTE RETROSPECTIF

Drug: Patient treated by Avapritinib in real life

Interventions

Patient treated by Avapritinib in real life DRUG

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 PROSPECTIF; COHORTE RETROSPECTIF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

Sponsors & Collaborators

• Centre Leon Berard: lead
• Blueprint Medicines Corporation: collaborator

Study Sites (7)

CHRU Besançon

Besançon, France

Location

Insitut Bergonié

Bordeaux, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut de Cancérologie de l'Ouest (ICO)

Nantes, France

Location

CHU Robert Debré

Reims, France

Location

Institut Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• MEHDI BRAHMI

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 15, 2021
• Study Start: March 31, 2021
• Primary Completion: April 30, 2024
• Study Completion: December 31, 2024
• Last Updated: December 26, 2023

Record last verified: 2023-12

Locations

FR (7)