Clinical Trials List
Protocol NumberPL3397-A-A103
NCT Number(ClinicalTrials.gov Identfier)NCT02734433
Completed
2016-06-01 - 2017-12-31
Phase I
Terminated1
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
A Phase 1 Study of Single Agent Pexidartinib in Asian Subjects With Advanced Solid Tumors
-
Trial Applicant
Daiichi Sankyo Taiwan Ltd.
-
Sponsor
Daiichi Sankyo Co. Ltd
-
Trial scale
Taiwan Single Center
-
Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
- James Chih-Hsin Yang Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Advanced Solid Tumors
Objectives
Primary Objectives:
• To assess the safety and tolerability of pexidartinib
in Asian subjects with advanced solid tumors
• To determine the recommended Phase 2 dose
(RP2D) of pexidartinib in Asian subjects with
advanced solid tumors
Secondary Objectives:
• To assess the pharmacokinetics (PK) profile of
pexidartinib
• To assess the pharmacodynamics (PD) effect of
pexidartinib on CSF-1 and adiponectin in plasma
• To evaluate the preliminary efficacy of pexidartinib
Test Drug
PLX3397 HCl Capsule, 200mg
Active Ingredient
Pexidartinib HCl(PLX3397)
Dosage Form
capsule
Dosage
200
Endpoints
Primary Outcome Measures :
1. Overall Response Based on RECIST V1.1 Following Oral Doses of Pexidartinib (Efficacy Analysis Set) [ Time Frame: Day 1 through Day 28 after last dose (within 18 months) ]
Secondary Outcome Measures :
1. Duration of Response or Duration of Stable Disease Following Oral Doses of Pexidartinib (Efficacy Analysis Set) [ Time Frame: Day 1 through Day 28 after last dose (within 18 months) ]
2. A Summary of Pexidartinib Pharmacokinetic Parameter (Cmax) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
3. A Summary of Pexidartinib Pharmacokinetic Parameter (AUC[0-8h]) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
4. A Summary of Pexidartinib Pharmacokinetic Parameter (Tmax) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
5. A Summary of Pexidartinib Pharmacokinetic Parameter (R[AUC]) by Cohort Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
6. A Summary of Pexidartinib Pharmacokinetic Parameter (R[Cmax]) by Cohort Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
7. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (AUC[0-8h]) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
8. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Cmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
9. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Tmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
10. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR AUC[0-8h]) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
11. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR Cmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
12. Number and Percentage of Participants With Common Treatment-emergent Adverse Events (TEAEs) (≥20%) Classified by Preferred Term (Safety Analysis Set) [ Time Frame: Baseline up to 18 months ]
13. Number and Percentage of Participants With Treatment-related TEAEs by Preferred Term (Safety Analysis Set) [ Time Frame: Baseline up to 18 months ]
1. Overall Response Based on RECIST V1.1 Following Oral Doses of Pexidartinib (Efficacy Analysis Set) [ Time Frame: Day 1 through Day 28 after last dose (within 18 months) ]
Secondary Outcome Measures :
1. Duration of Response or Duration of Stable Disease Following Oral Doses of Pexidartinib (Efficacy Analysis Set) [ Time Frame: Day 1 through Day 28 after last dose (within 18 months) ]
2. A Summary of Pexidartinib Pharmacokinetic Parameter (Cmax) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
3. A Summary of Pexidartinib Pharmacokinetic Parameter (AUC[0-8h]) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
4. A Summary of Pexidartinib Pharmacokinetic Parameter (Tmax) by Cohort and Day Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
5. A Summary of Pexidartinib Pharmacokinetic Parameter (R[AUC]) by Cohort Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
6. A Summary of Pexidartinib Pharmacokinetic Parameter (R[Cmax]) by Cohort Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
7. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (AUC[0-8h]) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
8. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Cmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
9. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Tmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
10. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR AUC[0-8h]) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
11. A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR Cmax) Following Oral Doses of Pexidartinib [ Time Frame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose ]
12. Number and Percentage of Participants With Common Treatment-emergent Adverse Events (TEAEs) (≥20%) Classified by Preferred Term (Safety Analysis Set) [ Time Frame: Baseline up to 18 months ]
13. Number and Percentage of Participants With Treatment-related TEAEs by Preferred Term (Safety Analysis Set) [ Time Frame: Baseline up to 18 months ]
Inclution Criteria
Inclusion Criteria:
Subjects must satisfy all of the following criteria to be
included in the study:
1. Age should be 20 years.
2. Subjects must have a pathologically documented solid
tumor that has relapsed from, or is refractory to
standard treatment, or for which no standard treatment
is available.
3. Women of childbearing potential must have a negative
serum pregnancy test within the 14-day period prior to
treatment allocation.
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
themselves, respectively, by using a highly effective
contraception method, as described below, throughout
the study and for up to 90 days after completion.
Highly effective methods of contraception include
hormonal methods associated with inhibition of
ovulation, intra-uterine device, surgical sterilization
(including partner’s vasectomy), or sexual abstinence.
5. Women of non-childbearing potential may be included
if they are either surgically sterile or have been
postmenopausal for ≥ 1 year. Women who have
documentation of at least 12 months of spontaneous
amenorrhea and have a follicle-stimulating hormone
(FSH) level > 40 mIU/mL will be considered
postmenopausal.
6. All associated toxicity from previous cancer therapy
must have been resolved (to ≤ Grade 1 or baseline)
prior to administration of pexidartinib.
7. Eastern Cooperative Oncology Group Scale of
Performance Status (ECOG PS) of 0 or 1.
8. Life expectancy ≥ 3 months, in the opinion of the
Investigator.
9. Adequate hematologic, hepatic, and renal function
defined by:
Absolute neutrophil count ≥ 1.5 × 109
/L
Platelet count ≥ 100 × 109
/L
Alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) ≤ 1.5 × upper limit of
normal (ULN) (if liver metastases are present,
≤ 3 x ULN)
Albumin ≥ 3 g/dL
Total bilirubin ≤ 1.5 × ULN
Hemoglobin > 9 g/dL
Serum creatinine ≤ 1.5 × ULN or calculated
creatinine clearance > 60 mL/min using the
Cockcroft-Gault formula
10. Adequate treatment washout period before registration
defined as:
Major surgery: ≥ 4 weeks (2 weeks for less
invasive surgery, such as colostomy)
Radiation therapy (eg, whole brain
radiotherapy): ≥ 4 weeks (if palliative
stereotactic radiation therapy, ≥ 2 weeks)
Chemotherapy or immunotherapy (including
targeted therapy with antibody or small
molecule, retinoid therapy, and hormonal
therapy): 4 weeks or 5 half-lives of the agent,
whichever is shorter (if the regimen has
contained nitrosoureas or mitomycin C,
≥ 6 weeks)
Other investigational drug therapy: ≥ 4 weeks
11. Willingness and ability to provide written informed
consent prior to any study-related procedures and to
comply with all study requirements.
Subjects must satisfy all of the following criteria to be
included in the study:
1. Age should be 20 years.
2. Subjects must have a pathologically documented solid
tumor that has relapsed from, or is refractory to
standard treatment, or for which no standard treatment
is available.
3. Women of childbearing potential must have a negative
serum pregnancy test within the 14-day period prior to
treatment allocation.
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
themselves, respectively, by using a highly effective
contraception method, as described below, throughout
the study and for up to 90 days after completion.
Highly effective methods of contraception include
hormonal methods associated with inhibition of
ovulation, intra-uterine device, surgical sterilization
(including partner’s vasectomy), or sexual abstinence.
5. Women of non-childbearing potential may be included
if they are either surgically sterile or have been
postmenopausal for ≥ 1 year. Women who have
documentation of at least 12 months of spontaneous
amenorrhea and have a follicle-stimulating hormone
(FSH) level > 40 mIU/mL will be considered
postmenopausal.
6. All associated toxicity from previous cancer therapy
must have been resolved (to ≤ Grade 1 or baseline)
prior to administration of pexidartinib.
7. Eastern Cooperative Oncology Group Scale of
Performance Status (ECOG PS) of 0 or 1.
8. Life expectancy ≥ 3 months, in the opinion of the
Investigator.
9. Adequate hematologic, hepatic, and renal function
defined by:
Absolute neutrophil count ≥ 1.5 × 109
/L
Platelet count ≥ 100 × 109
/L
Alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) ≤ 1.5 × upper limit of
normal (ULN) (if liver metastases are present,
≤ 3 x ULN)
Albumin ≥ 3 g/dL
Total bilirubin ≤ 1.5 × ULN
Hemoglobin > 9 g/dL
Serum creatinine ≤ 1.5 × ULN or calculated
creatinine clearance > 60 mL/min using the
Cockcroft-Gault formula
10. Adequate treatment washout period before registration
defined as:
Major surgery: ≥ 4 weeks (2 weeks for less
invasive surgery, such as colostomy)
Radiation therapy (eg, whole brain
radiotherapy): ≥ 4 weeks (if palliative
stereotactic radiation therapy, ≥ 2 weeks)
Chemotherapy or immunotherapy (including
targeted therapy with antibody or small
molecule, retinoid therapy, and hormonal
therapy): 4 weeks or 5 half-lives of the agent,
whichever is shorter (if the regimen has
contained nitrosoureas or mitomycin C,
≥ 6 weeks)
Other investigational drug therapy: ≥ 4 weeks
11. 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
Subjects who meet any of the following criteria will be
disqualified from entering the study:
1. Refractory nausea and vomiting, malabsorption,
external biliary shunt, or significant small bowel
resection that would have precluded adequate
absorption.
2. Presence of a medical or psychiatric condition that, in
the opinion of the Principal Investigator (PI), made the
subject inappropriate for inclusion in this study.
3. Previous use of pexidartinib or any biologic treatment
targeting colony stimulating factor-1 (CSF-1) or the
receptor for colony-stimulating factor-1 (CSF1R);
previous use of oral tyrosine kinase inhibitors, eg,
imatinib or nilotinib, is allowed.
4. Clinically active primary central nervous system tumors
or brain metastasis, defined as untreated and
symptomatic, or requiring therapy with steroids or
anticonvulsants to control associated symptoms.
5. Active or chronic infection with hepatitis C or known
positive hepatitis B surface antigen, or known active or
chronic infection with human immunodeficiency virus.
6. Known active tuberculosis.
7. Women who are breastfeeding.
8. A screening Fridericia corrected QT interval (QTcF)
≥ 450 ms (men) or ≥ 470 ms (women).
9. A medical history or complications of clinically
significant lung disease (eg, interstitial pneumonia,
pneumonitis, pulmonary fibrosis, and severe radiation
pneumonitis).
10. A history of symptomatic congestive heart failure
([CHF]; New York Heart Association [NYHA]
Classes II to IV) or serious cardiac arrhythmia requiring
treatment.
11. A history of myocardial infarction or unstable angina
within 6 months before enrollment.
12. An uncontrolled infection requiring intravenous
injection of antibiotics, antivirals, or antifungals.
Subjects who meet any of the following criteria will be
disqualified from entering the study:
1. Refractory nausea and vomiting, malabsorption,
external biliary shunt, or significant small bowel
resection that would have precluded adequate
absorption.
2. Presence of a medical or psychiatric condition that, in
the opinion of the Principal Investigator (PI), made the
subject inappropriate for inclusion in this study.
3. Previous use of pexidartinib or any biologic treatment
targeting colony stimulating factor-1 (CSF-1) or the
receptor for colony-stimulating factor-1 (CSF1R);
previous use of oral tyrosine kinase inhibitors, eg,
imatinib or nilotinib, is allowed.
4. Clinically active primary central nervous system tumors
or brain metastasis, defined as untreated and
symptomatic, or requiring therapy with steroids or
anticonvulsants to control associated symptoms.
5. Active or chronic infection with hepatitis C or known
positive hepatitis B surface antigen, or known active or
chronic infection with human immunodeficiency virus.
6. Known active tuberculosis.
7. Women who are breastfeeding.
8. A screening Fridericia corrected QT interval (QTcF)
≥ 450 ms (men) or ≥ 470 ms (women).
9. A medical history or complications of clinically
significant lung disease (eg, interstitial pneumonia,
pneumonitis, pulmonary fibrosis, and severe radiation
pneumonitis).
10. A history of symptomatic congestive heart failure
([CHF]; New York Heart Association [NYHA]
Classes II to IV) or serious cardiac arrhythmia requiring
treatment.
11. A history of myocardial infarction or unstable angina
within 6 months before enrollment.
12. An uncontrolled infection requiring intravenous
injection of antibiotics, antivirals, or antifungals.
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
0 participants
