Phase I Study of Preoperative Therapy Imatinib Mesylate and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor (GIST)
University of California, San Diego
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 (preoperative 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.
Description
Gastrointestinal stromal tumor (GIST) is the most common form of sarcoma. Surgical resection is the current main form of treatment, however preoperative medical therapies are also often necessary. The majority of gastrointestinal stromal tumor (approximately 60-70%) are caused by gain-of-function mutations in the KIT oncogene. Since KIT is a tyrosine kinase, it is not surprising that four of five Food and Drug Administration (FDA)-approved therapies for this condition are tyrosine kinase inhibitors that target the KIT oncogene. Among these compounds, imatinib is considered the standard first…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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, locally advanced, or metastatic gastrointestinal stromal tumor in any location that would benefit from preoperative therapy before tumor surgical resection * Has measurable or evaluable disease per Response Evaluation Criteria in Solid Tum…
Interventions
- DrugImatinib
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.
- DrugFampridine
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.
Location
- University of California, San DiegoLa Jolla, California