Oral Liporaxel (paclitaxel) treatment for gastrointestinal stromal tumors

A Phase II Study of Oral Paclitaxel (Liporaxel) in GIST Patients With a Low P-glycoprotein Expression After Failure With Imatinib, Sunitinib and Regorafenib

This study will test whether taking oral Liporaxel (a form of paclitaxel) can help people with advanced GIST who stopped responding to imatinib, sunitinib, and regorafenib and whose tumors have low P‑glycoprotein levels.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Drugs / interventions: imatinib, sunitinib, chemotherapy
• Locations: 1 site (Seoul, Songpagu)
• Trial ID: NCT06326346 on ClinicalTrials.gov

What this trial studies

This single-arm phase II trial gives oral Liporaxel (an oral paclitaxel formulation) to adults with metastatic or advanced GIST who have progressed after imatinib, sunitinib, and regorafenib. Patients must have tumor tissue showing low P‑glycoprotein expression (<6 by IHC), ECOG 0–2, at least one RECIST 1.1 measurable lesion, and adequate organ function. The study monitors safety and antitumor activity with scheduled imaging to measure response and progression-free survival and records adverse events using NCI-CTCAE v5.0. The trial builds on preclinical and earlier clinical signals that paclitaxel can be active in GIST, particularly in tumors with low P‑glycoprotein.

Who should consider this trial

Good fit: Adults (≥20 years) with histologically confirmed metastatic or advanced GIST (CD117+, DOG-1+, or KIT/PDGFRα mutation) who progressed on imatinib, sunitinib, and regorafenib, have low tumor P‑glycoprotein (<6), ECOG 0–2, measurable disease, and adequate organ function are ideal candidates.

Not a fit: Patients whose tumors have high P‑glycoprotein expression, who have not exhausted standard TKI options, or who have poor performance status (ECOG >2) or inadequate organ function are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, oral Liporaxel could provide a new, convenient chemotherapy option that shrinks tumors or delays progression for heavily pretreated GIST patients with low P‑glycoprotein.

How similar studies have performed: Earlier single-center phase II work with paclitaxel showed modest overall efficacy but better responses in patients with low P‑glycoprotein, and this oral Liporaxel approach builds on those promising subgroups.

Eligibility criteria

Inclusion Criteria:

1. Age 20 years or older, at the time of acquisition of informed consent
2. Histologically confirmed metastatic and/or advanced GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRα gene
3. Failed (progressed and/or intolerable) after prior treatments for GIST, including at least imatinib and sunitinib, regorafenib.
4. Adequate tissue obtained after treatment failure to imatinib, sunitinib, and regorafenib for P-glycoprotein immunohistochemistry (IHC) analysis, and showed P-glycoprotein expression of less than 6. (For patients with PDGFRα D842V mutation or other subtypes with poor response to tyrosine kinase inhibitors, tumor tissue obtained at any period can be used.)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0\~2
6. Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0
7. At least one measurable lesion as defined by RECIST version 1.1.
8. Adequate bone marrow, hepatic, renal, and other organ functions

   * Neutrophil \>1,500/mm3
   * Platelet \> 100,000/mm3
   * Hemoglobin \>8.0 g/dL
   * Total bilirubin \< 1.5 x upper limit of normal (ULN)
   * AST/ALT \< 2.5 x ULN
   * Creatinine \<1.5 x ULN
9. Life expectancy \> 12 weeks
10. Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imatinib and regorafenib need 1 week and sunitinib need 2 weeks.)
11. Provision of a signed written informed consent

Exclusion Criteria:

1. Women of child-bearing potential who are pregnant or breast feeding
2. Women or men who are not willing to use effective contraception entering the study period or until at least 3 months after the last study drug administration.
3. If any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, treatment required severe arrhythmia.
4. Uncontrolled infection
5. Diabetes mellitus with clinically significant peripheral artery disease
6. Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible)
7. Uncontrolled gastrointestinal toxicities with toxicity greater than NCI CTCAE grade 2
8. Acute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigator
9. The patient experienced any bleeding episode considered life-threatening, or any grade 3 or 4 bleeding event. (required transfusion or endoscopic or surgical intervention)
10. Patient who underwent major surgery or is under recovery from surgery within 28 days from the study treatment
11. Known diagnosis of HIV infection (HIV testing is not mandatory).
12. History of another primary malignancy that is currently clinically significant or currently requires active intervention.
13. Patients with clinically suspected brain metastasis symptom, brain metastases as assessed by radiologic imaging.
14. Alcohol or substance abuse disorder.
15. Known severe hypersensitivity to paclitaxel
16. Received paclitaxel-based treatment for GIST

Where this trial is running

Seoul, Songpagu

• Asan Medical Center, University of Ulsan College of Medicine — Seoul, Songpagu, South Korea (Recruiting)

Study contacts

• Study coordinator: Min-Hee Ryu, MD, PhD

Conditions Gastrointestinal Stromal Tumors