Resistance Profiling Using Functional Imaging and Next Generation Sequencing in Refractory Gastrointestinal Stomal Tumors (GIST)

NCT07109024 | Not Yet Recruiting

• 2 other identifiers: PATHFINDERS70116838
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Gastrointestinal stromal tumors (GIST) are the most common malignant sarcomas of the gastrointestinal tract. Inhibitors of the mutated driver proteins KIT and PDGFRA can temporarily control disseminated GIST disease but cannot cure it. Recently, the investigators were able to elucidate the two main resistance mechanisms-the coexistence of ATP-binding pocket (AP) and activation loop (AL) mutations, as well as AP/AL combination mutations. Determining these resistance factors requires methods that are not yet established in routine clinical practice. The investigators hypothesize that identifying these factors and creating resistance profiles in the context of the anatomical location of metastatic lesions can open up new, clinically relevant therapeutic options, including local therapies. The aim of this project is to evaluate the practicability of these methods in everyday clinical use. An AI-supported image analysis and specialized molecular methods will be combined into a comprehensive resistance profile and will be provided to the treating physicians to potentially guide treatment decisions.

Conditions

Gastrointestinal Stromal Tumor (GIST)

Keywords

GIST; Resistance; Ripretinib; Progression; Imaging

Outcome Measures

Primary Outcomes (1)

• Feasibility: Number of Patients with a PATHFINDER profile categorization within four weeks

  4 weeks

Secondary Outcomes (13)

• Technical feasibility: Turnaround-time required to provide the individual profile

  4-8 weeks

• Technical Feasibility: Practicality of sample collection

  4-8 weeks

• Clinical feasibility: Recruitment and retention rate

  3 years

• Clinical feasibility: Adherence to the diagnostic protocol

  2 years

• Economic endpoint: Expenses related to the diagnostic test

  3 years

Interventions

Generation of a comprehensive and single-lesion resistance profile DIAGNOSTIC_TEST

AI-supported image analysis of functional imaging (PET-CT) and previous imaging data and specialized molecular methods (next-generation sequencing) will be combined into a comprehensive resistance profile.

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

Patients with advanced gastrointestinal stromal tumors history of exposure and progression or intolerance to imatinib, sunitinib, regorafenib and ripretinib

You may qualify if:

• Advanced gastrointestinal stromal tumors history of exposure and progression or intolerance to imatinib, sunitinib, regorafenib and ripretinib
• Clinical indication for PET-CT and tumor biopsy (optional) (sarcoma center tumorboard protocol)
• Age 18 years and older
• FFPE tumor tissue available
• Previous imaging studies available (CT/MRI/PET Abdomen, ideally at baseline, best response and progression)
• ECOG ≤ 2
• Progressing tumor lesion(s) of which one is accessible for biopsy

You may not qualify if:

• contraindication for systemic TKI treatment
• contraindication for contrast-enhanced both CT and MRI imaging.
• GIST without KIT or PDGFRA mutations
• pregnant or breastfeeding women
• patient that - to the investigator's discretion - are not able or willing to comply with the provided protocol and visit schemes

Sponsors & Collaborators

• Universität Duisburg-Essen: lead
• University Hospital Münster, Insitute of Pathology: collaborator
• University Hospital Schleswig-Holstein: collaborator

Study Sites (2)

University Hospital Essen

Essen, 45122, Germany

Location

University Hospital Schleswig-Holstein, Dpt. of Hematlogy and Oncology

Lübeck, Germany

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples Tumor Samples (optional)

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Disease Progression

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Johanna Falkenhorst, MD

CONTACT

+40 201 723 2011; pathfinders@uk-essen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: August 7, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

DE (2)