Imatinib plus fampridine before surgery for KIT exon 11 gastrointestinal stromal tumor

Phase I Study of Neoadjuvant Therapy Imatinib Mesylate and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor (GIST)

This trial tests whether adding fampridine to standard imatinib before surgery is safe and helps shrink KIT exon 11 mutant GIST tumors in adults.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Diego (other)
• Drugs / interventions: imatinib, chemotherapy
• Locations: 1 site (La Jolla, California)
• Trial ID: NCT07171203 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 dose-finding trial giving fampridine together with standard-dose imatinib to adults with treatment-naïve KIT exon 11 mutant gastrointestinal stromal tumors prior to planned surgical resection. Participants take both drugs for at least two months (with the option to continue longer if tolerated) and attend scheduled clinic visits for safety labs, imaging, and other monitoring. The primary goal is to identify the maximum tolerated dose of fampridine when combined with imatinib and to document adverse events; secondary goals include preliminary signals of tumor response. Eligibility requires measurable disease, ECOG performance status 0–1, adequate organ function, and confirmation of a KIT exon 11 mutation by sequencing.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed, treatment-naïve, KIT exon 11 mutant localized or locally advanced GIST who are candidates for neoadjuvant therapy, have measurable disease, ECOG 0–1, and adequate organ function would qualify.

Not a fit: Patients without a KIT exon 11 mutation, those who have received prior tyrosine kinase inhibitors, have metastatic disease unsuitable for resection, poor performance status, or significant organ dysfunction are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could increase tumor shrinkage before surgery and potentially allow less extensive operations or better long-term outcomes.

How similar studies have performed: Imatinib is an established first-line drug for GIST, but combining it with a potassium-channel blocker like fampridine is a novel approach supported primarily by preclinical data rather than prior clinical success.

Eligibility criteria

Inclusion Criteria:

* Provision of written informed consent prior to any screening procedures
* Age ≥ 18 years
* Having been pathologically confirmed to have a KIT exon 11 mutant gastrointestinal stromal tumor assessed for KIT variant mutations by next generation sequencing
* Treatment naïve gastrointestinal stromal tumor
* Described as a primary localized or locally advance gastrointestinal stromal tumor in any location that would benefit from neoadjuvant therapy before tumor surgical resection
* Has measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors v1.1.
* Has Eastern Cooperative Oncology Group Performance Status of 0-1
* Has adequate hematologic, hepatic, and renal function: Absolute Neutrophil Count ≥ 1.5 x 10\^9/L; Hemoglobin ≥ 11 g/dL; Platelets ≥ 100 x 10\^9/L; Serum total bilirubin \< 2.0 x upper limit of normal; Aspartate aminotransferase and alanine aminotransferase ≤ 5 x upper limit of normal; Plasma creatinine phosphokinase \< 1.5 x upper limit of normal; Serum creatinine ≤ 1.0 x upper limit of normal or calculated creatinine clearance ≥ 50ml/min based upon the Cockcroft-Gault Equation
* Life expectancy of ≥ 5 years
* Participants able to cause pregnancy agree to use an adequate method of contraception starting with the first dose of study therapy and for 120 days after the last dose

Exclusion Criteria:

* Unwilling or unable to comply with the protocol
* KIT exon 9, 13, 14, 17, or 18 mutant gastrointestinal stromal tumor by next generation sequencing.
* Non-KIT mutant gastrointestinal stromal tumor
* Newly diagnosed with metastatic gastrointestinal stromal tumor
* Have residual tumor following surgical debulking
* Have had major surgery within 4 weeks of initiation of study medication.
* Of childbearing potential
* Pregnant or nursing.
* Received imatinib monotherapy prior to the first dose of study treatment with imatinib plus fampridine and has demonstrated tumor shrinkage in computed tomography assessment images.
* Received fampridine prior to the first dose of study treatment with imatinib plus fampridine.
* Use of compounded fampridine or other forms of fampridine.
* Known brain metastases and any other progressive neurologic dysfunction should be excluded from this clinical trial because of their poor prognosis and because their progressive neurologic dysfunction would confound the evaluation of neurologic and other adverse events.
* Evidence of severe or uncontrolled systemic diseases (e.g., unstable, or uncompensated respiratory, cardiac \[including life threatening arrhythmias\] disease).
* Presence of cardiac impairment defined as:
* Prior history of cardiovascular disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions; OR
* History of myocardial infarction/active ischemic heart disease within one year of study entry; OR
* Uncontrolled dysrhythmias; OR
* Poorly controlled angina.
* Unresolved toxicity Common Terminology Criteria Adverse Events (CTCAE) Grade ≥ 2 from previous anti-cancer therapy.
* Allergy or sensitivity to fampridine or known allergies to aminopyridine products, which in the opinion of the investigator(s) suggests an increased potential for an adverse hypersensitivity to fampridine.
* Allergy to imatinib.
* Any chronic liver disease including, but not limited to cirrhosis, non-alcoholic steatohepatitis, alcohol-related liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, hepatic, or biliary autoimmune disorders (i.e., primary biliary cholangitis, autoimmune hepatitis). Exception: Patients aged ≤ 65 years with non-alcoholic fatty liver disease detected by imaging are acceptable if adequate hepatic function as defined in the inclusion criteria is confirmed. Note: Patients aged \> 65 years with non-alcoholic fatty liver disease are excluded from the study.
* Any evidence or history of hepatitis B and/or hepatitis C.
* Medical condition such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease that, in the opinion of the investigator(s), would make this study unreasonably hazardous for the patient.
* Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the investigator(s) likely might compromise the safety of the participant or the integrity of the study, interfere with the participant participation in the trial, or compromise the trial objectives.
* History of seizures.
* Cannot swallow oral formulations of the medications or lack physical integrity of the upper gastrointestinal tract, or has known malabsorption syndromes. Note: imatinib tablets can be dissolved in water or apple juice if participants have difficulty swallowing.
* Have taken part in an experimental drug study within 4 weeks of initiating study treatment with imatinib plus fampridine
* Receiving other anti-neoplastic therapy (e.g., chemotherapy, targeted therapy, or radiotherapy) concurrently or within 4 weeks of starting study treatment with imatinib plus fampridine
* Receiving medications that inhibit the renal Organic Cation Transporter 2 (OCT2), such as cimetidine and quinidine, because of possible drug-drug interactions.
* Receiving medications known to be strong inhibitors or inducers of CYP3A4/5.
* Receiving medications known to be strong inhibitors or inducers of cytochrome CYP2E1 or medications metabolized by cytochrome CYP2B6 or CYP2C9/19 that have narrow therapeutic index and that cannot be discontinued before starting study treatment.

Where this trial is running

La Jolla, California

• University of California, San Diego — La Jolla, California, United States (RECRUITING)

Study contacts

• Principal investigator: Paul Fanta, MD — University of California, San Diego
• Study coordinator: Paul Fanta, MD

Conditions: Gastrointestinal Stromal Tumors, imatinib, fampridine, 4-aminopyridine, gastrointestinal stromal tumor, phase 1 trial, KIT exon 11 mutant, voltage-gated potassium channel blocker