Gastrointestinal Stromal TumorsPhase 1NCT07171203
Preoperative Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor
A Phase 1 study testing Imatinib and Fampridine in people with Gastrointestinal Stromal Tumors, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Imatinib and Fampridine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2026to Jul 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 Tumors v1.1.
Show all 10Show fewer
- 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
Who cannot join
- 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
- Have residual tumor following surgical debulking
- Have had major surgery within 4 weeks of initiation of study medication.
- Of childbearing potential
Show all 31Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Diego
La Jolla, California, 92093
Paul Fanta, MD, 858-822-5354, CancerCTO@health.ucsd.edu
Gastrointestinal Research Team, 858-822-5354, CancerCTO@health.ucsd.edu
About this study
Official title: Phase I Study of Preoperative Therapy Imatinib Mesylate and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor (GIST)
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:
Read more
- 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.
Read the detailed 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 line treatment. However, tumor response to tyrosine kinase inhibitors is suboptimal and more efficacious therapies are needed.
There are data that demonstrate lack of KIT protein expression in some KIT mutant gastrointestinal stromal tumor cells (cell not expressing KIT are referred to as KITnegative/low). Therefore, these cells do not have the cellular machinery that would allow them to respond to tyrosine kinase inhibitors.
The study investigators have discovered that the mRNA for the beta subunit of the voltage-gated potassium channels (VGKCs), Kvβ1.1, is expressed at high levels in KITnegative/low tumor cells. Previous studies have also shown that inhibition of the voltage-gated potassium channels (VGKCs) can inhibit cell proliferation and migration/invasion, as well as induce apoptosis in various cancer types. This led to the hypothesis that inhibitors of voltage-gated potassium channels (VGKCs) may have antitumor activity in KITnegative/low gastrointestinal stromal tumor cells.
A voltage-gated potassium channels inhibitor, fampridine, is FDA-approved for multiple sclerosis. The investigators hypothesize that voltage-gated potassium channels (VGKCs) blockade with fampridine may represent a novel strategy for treating KITnegative/low gastrointestinal stromal tumor. The investigators performed preclinical studies that suggest that the combination imatinib plus fampridine may lead to cell killing in an additive and/or synergistic manner in vitro. In addition, they showed that imatinib synergizes with fampridine to decrease tumor mass in vivo in a genetically engineered mouse model of GIST that carry KIT exon 11 Val-558 deletion.
Thus, the investigators aim to conduct this single site, prospective, open-label, non-randomized, single-arm phase 1 clinical trial in patients with KIT exon 11 mutant gastrointestinal stromal tumor to evaluate the safety and tolerability of the combination of imatinib plus fampridine in the preoperative setting (before surgery) to establish the dose of fampridine that can be used in a future phase 2 trial.
The recommended phase 2 dose (RP2D) will be determined based on the rate of dose limiting toxicities (DLT) using the standard 3+3 phase 1 trial design with 3 dose levels.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Imatinib, Fampridine
- Keywords
- imatinib, fampridine, 4-aminopyridine, gastrointestinal stromal tumor, phase 1 trial, KIT exon 11 mutant, voltage-gated potassium channel (VGKC) blocker
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Also called Imatinib mesylate, Gleevec
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.
FampridineDrug
Also called Dalfampridine, Ampyra, Fampyra, 4-Aminopyridine
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Imatinib; Drug: Fampridine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start13 May 2026
- Primary completionJul 2030 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Fanta, University of California, San Diego
- Investigators
- Paul Fanta, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07171203
- Sponsor's protocol ID
- 811484
- Status last verified
- May 2026
- First submitted
- 5 Sep 2025
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Preoperative Therapy Imatinib Mesylate and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor (GIST)
- ClinicalTrials.gov ID
- NCT07171203
- Acronym / sponsor ID
- 811484
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 13 May 2026 (actual)
- Primary completion
- Jul 2030 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 12 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 line treatment. However, tumor response to tyrosine kinase inhibitors is suboptimal and more efficacious therapies are needed.
There are data that demonstrate lack of KIT protein expression in some KIT mutant gastrointestinal stromal tumor cells (cell not expressing KIT are referred to as KITnegative/low). Therefore, these cells do not have the cellular machinery that would allow them to respond to tyrosine kinase inhibitors.
The study investigators have discovered that the mRNA for the beta subunit of the voltage-gated potassium channels (VGKCs), Kvβ1.1, is expressed at high levels in KITnegative/low tumor cells. Previous studies have also shown that inhibition of the voltage-gated potassium channels (VGKCs) can inhibit cell proliferation and migration/invasion, as well as induce apoptosis in various cancer types. This led to the hypothesis that inhibitors of voltage-gated potassium channels (VGKCs) may have antitumor activity in KITnegative/low gastrointestinal stromal tumor cells.
A voltage-gated potassium channels inhibitor, fampridine, is FDA-approved for multiple sclerosis. The investigators hypothesize that voltage-gated potassium channels (VGKCs) blockade with fampridine may represent a novel strategy for treating KITnegative/low gastrointestinal stromal tumor. The investigators performed preclinical studies that suggest that the combination imatinib plus fampridine may lead to cell killing in an additive and/or synergistic manner in vitro. In addition, they showed that imatinib synergizes with fampridine to decrease tumor mass in vivo in a genetically engineered mouse model of GIST that carry KIT exon 11 Val-558 deletion.
Thus, the investigators aim to conduct this single site, prospective, open-label, non-randomized, single-arm phase 1 clinical trial in patients with KIT exon 11 mutant gastrointestinal stromal tumor to evaluate the safety and tolerability of the combination of imatinib plus fampridine in the preoperative setting (before surgery) to establish the dose of fampridine that can be used in a future phase 2 trial.
The recommended phase 2 dose (RP2D) will be determined based on the rate of dose limiting toxicities (DLT) using the standard 3+3 phase 1 trial design with 3 dose levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib plus Fampridine | Experimental | Drug: Imatinib, Drug: FampridineImatinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (31 listed)
- 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
- Have residual tumor following surgical debulking
- Have had major surgery within 4 weeks of initiation of study medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImatinibAlso: Imatinib mesylate, GleevecTyrosine 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. | Drug | Imatinib plus Fampridine |
| FampridineAlso: Dalfampridine, Ampyra, Fampyra, 4-AminopyridineVoltage-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. | Drug | Imatinib plus Fampridine |
Primary outcome
Recommended phase 2 dose
Time frame: 28 days
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Fanta, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib and Fampridine in people with Gastrointestinal Stromal Tumors, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paul Fanta, MD ((858) 822-5354, cancerCTO@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.