Phase 2 Study to Evaluate the Efficacy of Regorafenib in Specific GIST Mutation Subsets (KIT Exon 17, 18, or 14 Mutation and SDHB Deficient GIST) in the Post-imatinib Second-line Setting.

Phase 2 Study to Evaluate the Efficacy of Regorafenib in Specific GIST Mutation Subsets (KIT Exon 17, 18, or 14 Mutation and SDHB Deficient GIST) in the Post-imatinib Second-line Setting.

Gastrointestinal Stromal Tumor

Recruiting

2

Start Date 06/18/2024

Age of Trial (yrs) 1

Gleevec-resistant

SDH-directed

Block KIT/PDGFRA

Specifically GIST and only GIST

2023-0390 NCI-2023-08857

M.D. Anderson Cancer Center

Neta Somaiah, MD 713-792-3626 nsomaiah@mdanderson.org

Oral

Study Overview
Brief Summary
To learn if regorafenib can help to control the disease.

Primary Objectives:

To assess efficacy of regorafenib in second-line GIST for patients with KIT exon 17, 18, or 14 mutation and SDHB deficient who progressed on imatinib as measured by PFS (RECIST 1.1).

Secondary Objectives:

RR by RECIST 1.1 and CHOI criteria
Progression-free rate at 1 year and 2 years
Median OS and OS at 1 years, 2years, and 5 years

Exploratory objectives:

Resistance mechanism (ctDNA analysis) in patients initially responding to regorafenib
Response data on next line of treatment post regorafenib

Partial Eligibility Criteria here below (See NCT listing for full eligibility (inclusion/exclusion) criteria)

Eligibility:

Inclusion Criteria:

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.

Age ≥18 years.
Histologic diagnosis of GIST with presence of KIT exon 17, 18, or 14 mutation, or SDHB deficiency on tumor biopsy and/ or liquid biopsy.
Participants must have unresectable or metastatic GIST and radiologic progression on imatinib treatment. Imatinib treatment must have been discontinued at least 5 days prior to the first dose of study drug. All imatinib treatment will be counted as 1 line of therapy.
ECOG performance status ≤2 (Karnofsky ≥60%) at screening.
Life expectancy of at least 12 weeks (3 months).

Exclusion Criteria

Patients who had received treatment with TKI other than imatinib.
Patients with pheochromocytoma.