Clinical Trials List
Protocol NumberPL3397-A-U126
NCT Number(ClinicalTrials.gov Identfier)NCT03291288
Completed
2017-08-01 - 2018-12-31
Others
Terminated1
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients
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Trial Applicant
Daiichi Sankyo Taiwan Ltd.
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Sponsor
Daiichi Sankyo Inc.
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
- Chih-Hung Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Advanced Solid Tumors
Objectives
This study has two parts.
Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents.
Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types.
In Part 2, the same participants will continue to receive pexidartinib twice daily.
Participants will be allowed to continue using pexidartinib as long as the participant derives benefit.
Test Drug
Pexidartinib (PLX3397)
Active Ingredient
Pexidartinib HCl
Dosage Form
capsule
Dosage
200mg
Endpoints
Primary Endpoints
PK parameters of midazolam and S-warfarin: Cmax, tmax, and AUClast. If data permits,
other PK parameters including t1/2 and AUCinf will be calculated.
Secondary Endpoints
PK
Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for
pexidartinib and its metabolite, ZAAD-1006a
Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for
midazolam metabolite, 5-hydroxy midazolam and also metabolite to parent
ratio (MPR) for 5-hydroxy midazolam and midazolam will be calculated
Efficacy
Best objective response per RECIST 1.1
Duration of response
Time to progression (for TGCT and other non-malignant tumors)
Progression-free survival (for malignant tumors)
Safety
TEAEs
Vital signs
Electrocardiograms (ECGs)
Clinical laboratory tests including AST/ALT/Total bilirubin (TBil)
Exploratory Endpoints
PGx biomarkers
Optional: PDy biomarkers
Optional: Tumor biomarker analysis
PK parameters of midazolam and S-warfarin: Cmax, tmax, and AUClast. If data permits,
other PK parameters including t1/2 and AUCinf will be calculated.
Secondary Endpoints
PK
Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for
pexidartinib and its metabolite, ZAAD-1006a
Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for
midazolam metabolite, 5-hydroxy midazolam and also metabolite to parent
ratio (MPR) for 5-hydroxy midazolam and midazolam will be calculated
Efficacy
Best objective response per RECIST 1.1
Duration of response
Time to progression (for TGCT and other non-malignant tumors)
Progression-free survival (for malignant tumors)
Safety
TEAEs
Vital signs
Electrocardiograms (ECGs)
Clinical laboratory tests including AST/ALT/Total bilirubin (TBil)
Exploratory Endpoints
PGx biomarkers
Optional: PDy biomarkers
Optional: Tumor biomarker analysis
Inclution Criteria
Inclusion Criteria
Patients must meet the following inclusion criteria to be enrolled in the study:
1. Age 18 y or the legal age for being considered as an adult in the country
where the patient is screened at the time of signing informed consent.
2. A diagnosis of TGCT, kit-mutant melanoma, kit-mutant GIST, leukemia, or other
tumor for which there is no other standard systemic therapy. Patients with TGCT
or other non-malignant tumor must be approved by the Sponsor prior to Screening
and enrollment. Prior pexidartinib is permitted for TGCT patients unless
ineffective or not related and there has been a washout period of at least 4 wk.
3. Women of childbearing potential must have a negative serum pregnancy test
within 14 d prior to enrollment. (Where demanded by local regulations, this test
may be required within 72 h prior to enrollment).
4. Men and women of childbearing potential are permitted in the study as long as
they consent to avoid getting their partner pregnant or becoming pregnant,
respectively, by using a highly effective contraception method, as described
below, throughout the study and up to 90 d after completion. Highly effective
methods of contraception include intra-uterine device (nonhormonal or
hormonal); bilateral tubal occlusion; vasectomy; sexual abstinence (only if this is
in line with the patient’s current lifestyle); or barrier methods (eg, condom,
diaphragm) used in combination with hormonal methods associated with
inhibition of ovulation. Women of nonchildbearing potential may be included if
they are either surgically sterile or have been postmenopausal for ≥ 1 y. Women
who have documentation of at least 12 mo of spontaneous amenorrhea and have a
follicle-stimulating hormone level > 40 mIU/mL will be considered
postmenopausal.
5. Adequate hematologic, hepatic, and renal function, defined by:
Absolute neutrophil count ≥ 1.5 × 109
/L
Hemoglobin > 10 g/dL
Platelet count ≥ 100 × 109
/L
AST and ALT ≤ 1.5 × upper limit of normal (ULN)
TBil ≤ ULN with an exception of patients with confirmed Gilbert’s syndrome.
For patients with confirmed Gilbert’s syndrome, the TBil should be
≤ 1.5 × ULN
Serum creatinine ≤ 1.5 × ULN
6. Willingness and ability to use a pill diary.
7. Willingness and ability to provide written informed consent prior to any
study-related procedures and to comply with all study requirements.
Patients must meet the following inclusion criteria to be enrolled in the study:
1. Age 18 y or the legal age for being considered as an adult in the country
where the patient is screened at the time of signing informed consent.
2. A diagnosis of TGCT, kit-mutant melanoma, kit-mutant GIST, leukemia, or other
tumor for which there is no other standard systemic therapy. Patients with TGCT
or other non-malignant tumor must be approved by the Sponsor prior to Screening
and enrollment. Prior pexidartinib is permitted for TGCT patients unless
ineffective or not related and there has been a washout period of at least 4 wk.
3. Women of childbearing potential must have a negative serum pregnancy test
within 14 d prior to enrollment. (Where demanded by local regulations, this test
may be required within 72 h prior to enrollment).
4. Men and women of childbearing potential are permitted in the study as long as
they consent to avoid getting their partner pregnant or becoming pregnant,
respectively, by using a highly effective contraception method, as described
below, throughout the study and up to 90 d after completion. Highly effective
methods of contraception include intra-uterine device (nonhormonal or
hormonal); bilateral tubal occlusion; vasectomy; sexual abstinence (only if this is
in line with the patient’s current lifestyle); or barrier methods (eg, condom,
diaphragm) used in combination with hormonal methods associated with
inhibition of ovulation. Women of nonchildbearing potential may be included if
they are either surgically sterile or have been postmenopausal for ≥ 1 y. Women
who have documentation of at least 12 mo of spontaneous amenorrhea and have a
follicle-stimulating hormone level > 40 mIU/mL will be considered
postmenopausal.
5. Adequate hematologic, hepatic, and renal function, defined by:
Absolute neutrophil count ≥ 1.5 × 109
/L
Hemoglobin > 10 g/dL
Platelet count ≥ 100 × 109
/L
AST and ALT ≤ 1.5 × upper limit of normal (ULN)
TBil ≤ ULN with an exception of patients with confirmed Gilbert’s syndrome.
For patients with confirmed Gilbert’s syndrome, the TBil should be
≤ 1.5 × ULN
Serum creatinine ≤ 1.5 × ULN
6. Willingness and ability to use a pill diary.
7. Willingness and ability to provide written informed consent prior to any
study-related procedures and to comply with all study requirements.
Exclusion Criteria
Exclusion Criteria
Patients must not meet the following exclusion criteria to be enrolled in the study:
1. Known active or chronic human immunodeficiency virus (HIV) or hepatitis C
virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen.
2. Known active tuberculosis.
3. Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis,
inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic
reasons. Gilbert’s disease is allowed if TBil is ≤ 1.5 × ULN.
4. Women who are breastfeeding.
5. Patients with a poor metabolizer status of CYP2C9.
6. Patients on potent CYP2C9, CYP3A4, and Uridine 5'-diphosphoglucuronosyltransferase family 1 member A4 (UGT1A4) inducer and inhibitors
and potent P-glycoprotein (P-gp) inhibitors and inducers, unless these
medications are discontinued at least 14 d before study drug administration. Food
or beverages containing CYP3A4/5 inhibitors (eg, grapefruit, pomegranate,
pomelo, and star fruit) should be avoided throughout the study.
7. A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms
(women).
8. History of hypersensitivity to any investigational products, including their
excipients.
9. Inability to swallow capsules.
10. Inability to complete study procedures.
11. Patients on warfarin or midazolam and unable to change to alternate
therapy. Prior therapy with warfarin or midazolam is allowed with a
washout period of at least 4 wk.
12. Patients with abnormal PT/INR values or contraindications for warfarin or
midazolam.
Patients must not meet the following exclusion criteria to be enrolled in the study:
1. Known active or chronic human immunodeficiency virus (HIV) or hepatitis C
virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen.
2. Known active tuberculosis.
3. Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis,
inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic
reasons. Gilbert’s disease is allowed if TBil is ≤ 1.5 × ULN.
4. Women who are breastfeeding.
5. Patients with a poor metabolizer status of CYP2C9.
6. Patients on potent CYP2C9, CYP3A4, and Uridine 5'-diphosphoglucuronosyltransferase family 1 member A4 (UGT1A4) inducer and inhibitors
and potent P-glycoprotein (P-gp) inhibitors and inducers, unless these
medications are discontinued at least 14 d before study drug administration. Food
or beverages containing CYP3A4/5 inhibitors (eg, grapefruit, pomegranate,
pomelo, and star fruit) should be avoided throughout the study.
7. A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms
(women).
8. History of hypersensitivity to any investigational products, including their
excipients.
9. Inability to swallow capsules.
10. Inability to complete study procedures.
11. Patients on warfarin or midazolam and unable to change to alternate
therapy. Prior therapy with warfarin or midazolam is allowed with a
washout period of at least 4 wk.
12. Patients with abnormal PT/INR values or contraindications for warfarin or
midazolam.
The Estimated Number of Participants
-
Taiwan
5 participants
-
Global
30 participants
