Paclitaxel in patients with GIST with low P-glycoprotein expression after failure of at least imatinib and sunitinib, and regorafenib.

Not Applicable

Recruiting

• Conditions: Neoplasms

• Registration Number: KCT0003895
• Lead Sponsor: Asan Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 January 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1)A patient aged =20 years when he/she fills in informed consent form (ICF)
2)Patients who have mutation of CD117(+), DOG-1(+), or KIT or PDGFRa genes and are histologically diagnosed with metastatic and/or advanced (unresectable or relapsing) GIST
3)Patients who failed in previous treatments for GIST, all inclusive of imatinib, sunitinib, and regorafenib (disease progression and/or intolerable) (Note: The number of treatments who might have received previously is not limited. Previous use of other chemotherapies concurrently used with tyrosine kinase inhibitor (TKI), or imatinib, sunitinib, and regorafenib is permitted.)

Disease progression is defined as follows:
(1) Increase of tumor size by more than 20% according to RECIST Version 1.1,
(2) Appearance of a clear new lesion (except a small cystic lesion in the liver which occurred
newly within 6 months after starting TKI)
(3) A new solid node located in the cystic mass, or
(4) Increase of existing solid node located in the cystic mass (> 20%).

Intolerability to previous TKI is defined as follows:
(1) Less than 75% of medication compliance due to non-hematological toxicity of Level 2 or above despite dose reduction to one-step lower level (300 mg/day for imatinib; 37.5 mg/day with 4-week administration/2-week withdrawal or 25 mg/day with successive administration for sunitinib; and 120 mg/day for regorafenib)
(2) Febrile neutropenia, Grade 4 neutropenia lasting >6 days, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia accompanied with clinically significant hemorrhage, Grade 3-4 or intolerable continuous Grade 2 non-hematologic toxicity despite dose reduction to one-step lower level as described above.
4)P-glycoprotein immunohistochemistry (IHC) H-score =250 in tumor tissue obtained after failure in previous treatment for GIST, including imatinib, sunitinib, and regorafenib
: H-score is a sum of the muliplications of each intensity (0–3) of P-glycoprotein measured by IHC by proportion (0–100) of tumor cells which indicates the relevant intensity (0-300).
: Intensity is evaluated at 0 (negative), 1 (weak), 2 (moderate), or 3 (strong).
: e.g.) If proportion with 3 of intensity of P-glycoprotein is 40%, proportion with 2 is 30%, proportion with 1 is 20%, and proportion with 0 is 10%, H-score is 200 in 3x40 + 2x30 + 1x20”
5)ECOG performance status of 0~2
6)Toxicity of all previous treatments is recovered to Grade 0 or Grade 1 according to NCI-CTCAE Version 5.0
7)There is at least one measurable lesion as defined under RECIST Version 1.1.
8)The functions of bone marrow, liver, kidney and other organs are proper:
- Neutrocyte = 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 (or = 5 x ULN if there is metastasis)
- Creatinine =1.5 x ULN
9)=12 weeks of life expectancy
10)A washout period of previous TKI or chemotherapy must exceed 4 times of the half life (For imatinib, sunitinib and regorafenib, one week of wash out period is enough.)
11)Patients who signed ICF

Exclusion Criteria

1)Pregnant or nursing women, or women of childbearing age
2)A woman or a man who is not willing to use effective contraception during study drug administration or within 3 months following end of study drug administration
-Barrier method should be used both in men and women during study drug administration and up to 3 months following end of administration. Oral preparations, implants, or contraceptive injections are not deemed as effective contraceptions in this study since these may be influenced by cytochrome P450 interactions.
-Women of childbearing age are defined as sexually mature women who have not received hysterectomy or do not undergo natural menopause for more than 12 consecutive months, at least (that is, who had the menses within previous 12 months), and must be shown to be negative in serum or urine pregnancy test within 14 days before starting paclitaxel treatment.
3)If a patient falls under one of the followings within 6 months prior to recruitment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attacks, serious cardiac arrhythmia requiring treatment
4)Uncontrolled infection
5)Diabetes with sign of clinically significant peripheral disease
6)Acute or chronic liver disease and all chronic hepatic impairments (A patient with stable chronic hepatitis B is eligible.
7)Uncontrolled gastrointestinal toxicity (nausea, diarrhea, vomiting) accompanied with toxicity
above NCI CTCAE Grade 2
8) Other severe acute or chronic internal diseases or mental diseases, or abnormal laboratory values that might increase risks associated with study participation or study drug administration or interfere with analysis of study results, or make study participation by a patient inappropriate according to investigator’s judgment
9) A patient who has hemorrhage that is thought to threaten one’s life requiring transfusion or endoscopic or surgical intervention, or Grade 3 or 4 hemorrhage within 3 months prior to treatment with study drug
10)A patient who has received major operation in 28 days prior to treatment with study drug, or has not recovered from adverse reactions following the treatment
11)If diagnosis of HIV infection is known (HIV test is not obligatory)
12)History of other primary malignant tumor that has become clinically significant recently, or requires active intervention currently
13)A patient with brain metastasis when evaluated by radiological imaging (e.g. CT, MRI) if there is a symptom that is clinically suspected of brain metastasis
14)Alcohol or substance abuse disorder

Study & Design

• Study Type: Interventional Study
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Disease control rate

Secondary Outcome Measures

Name	Time	Method
Progression-free survival