Neoadjuvant Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor

NCT07171203 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 811484
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn what dose of the drug fampridine can be given safely together with imatinib (Gleevec) in patients with gastrointestinal stromal tumor (GIST) with a DNA mutation in exon 11 of the KIT gene. The main questions this study aims to answer are:

• What is the maximum dose of fampridine that can be given safely together with imatinib (Gleevec)?
• Is the combination of the two drugs efficacious against the tumor? Participants will:
• Take the drugs before tumor surgery (neoadjuvant treatment) for at least 2 months with the option to continue for a longer period of time if treatment seems safe and effective.
• Visit the clinic at the scheduled appointments for checkups and tests.

Conditions

Gastrointestinal Stromal Tumors

Keywords

imatinib; fampridine; 4-aminopyridine; gastrointestinal stromal tumor; phase 1 trial; KIT exon 11 mutant; voltage-gated potassium channel (VGKC) blocker

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose

  Recommended phase 2 dose (RP2D) of imatinib plus fampridine determined by the dose-limiting toxicities and maximum tolerated dose via assessment of adverse events as defined by CTCAE version 5.0 during the first cycle (28 days) of therapy.

  28 days

Study Arms (1)

Imatinib plus Fampridine

EXPERIMENTAL

Imatinib in combination with fampridine at one of three dose levels (10 mg every other day, or 10 mg every day, or 10 mg twice a day) after a 7-day run-in period with imatinib monotherapy.

Drug: Imatinib; Drug: Fampridine

Interventions

Fampridine DRUG

Voltage-gated potassium channel (VGKC) blocker. Fampridine will be dosed in a 3+3 design at 10 mg given either every 2 days, or every day, or twice a day.

Also known as: Dalfampridine, Ampyra, Fampyra, 4-Aminopyridine

Imatinib plus Fampridine

Imatinib DRUG

Tyrosine kinase inhibitor. Imatinib will be dosed at 400 mg once a day. Dose can be reduced by 100 mg per dose reduction step if clinically indicated.

Also known as: Imatinib mesylate, Gleevec

Imatinib plus Fampridine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate; 4-Aminopyridine

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Aminopyridines; Amines; Pyridines

Study Officials

• Paul Fanta, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Fanta, MD

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Jason Sicklick, MD

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor, medical oncology

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 12, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2031
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)