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
- Conditions
- Cancerneoplasms10040776
- Registration Number
- NL-OMON55479
- Lead Sponsor
- Daiichi Pharmaceutical
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
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.DA histopathologically diagnosed tumor as follows: a.DTenosynovial giant cell
tumor (TGCT), which is associated with severe morbidity or functional
limitations and for whom surgery is not an option. Prior pexidartinib is
permitted for TGCT patients unless ineffective or not tolerated and there has
been a washout period of at least 4 weeks.
b.DKIT-mutant tumor, including melanoma or gastrointestinal stromal tumor
(GIST), for which there is no standard systemic therapy.
c.DOther solid tumors (all comers) for which there is no standard systemic
therapy and there is a rationale for use of pexidartinib at the Investigator's
discretion.
3.DWomen 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.DMen 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. The cut-off for performing a follicle- stimulating hormone test
is * 50 years old.
5.DAdequate hematologic, hepatic, and renal function, defined by:
*DAbsolute neutrophil count * 1.5 × 109/L.
*DHemoglobin > 10 g/dL.
*DPlatelet count * 100 × 109/L.
*DAspartate aminotransferase (AST) and alanine aminotransferase
(ALT) * upper limit of normal (ULN).
*DTotal bilirubin (TBil) and direct bilirubin (DBil) * ULN with an exception of
patients with confirmed Gilbert's syndrome. For patients with confirmed
Gilbert's syndrome, the total bilirubin should be * 1.5 × ULN.
*DSerum creatinine * 1.5 × ULN.
6.DWillingness and ability to use a paper pill diary.
7.DWillingness and ability to provide written informed consent prior to any
study-related procedures and to comply with all study requirements.
1.Known active or chronic human immunodeficiency virus (HIV) or hepatitis C
virus (HCV) infection, or positive hepatitis B (HepB) surface antigen. Prior
hepatitis infection that has been treated with highly effective therapy with no
evidence of residual infection and with normal liver function (ALT, AST, total
and direct bilirubin * ULN) is allowed.
2.DKnown active tuberculosis.
3.DHepatobiliary 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 poor metabolizer status of cytochrome P450 (CYP)
2C9.
6.Patients on potent CYP2C9, CYP3A4, and uridine 5' diphospho-
glucuronosyltransferase (UDGT) 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. Foods or beverages containing CYP3A4/5 inhibitors (eg,
grapefruit, pomegranate, pomelo, and star fruit) should be avoided throughout
the study.
7.Anti-tumor or investigational agent therapy within 4 weeks prior to
Day 1.
8.A screening Fridericia-corrected QT (QTcF) interval * 450 ms (men)
or * 470 ms (women).
9.History of hypersensitivity to any investigational products, including their
excipients.
10.Inability to swallow oral medication.
11.Inability to complete study procedures.
12.Patients on tolbutamide or midazolam and unable to change to alternate
therapy. Prior therapy with tolbutamide or midazolam is allowed with a washout
period of at least 4 wk.
13.Patients with contraindications for tolbutamide or midazolam
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PK parameters of midazolam and tolbutamide: Cmax, tmax, and AUClast. If data<br /><br>permits,<br /><br>other PK parameters including t1/2 and AUCinf will be calculated.</p><br>
- Secondary Outcome Measures
Name Time Method <p>PK<br /><br>- Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for<br /><br>pexidartinib and its metabolite, ZAAD-1006a<br /><br>- Plasma PK parameters (Cmax, Tmax, AUClast) will be calculated for<br /><br>midazolam metabolite, 5-hydroxy midazolam and also metabolite to parent<br /><br>ratio (MPR) for 5-hydroxy midazolam and midazolam will be calculated<br /><br><br /><br>Efficacy<br /><br>- Best objective response per RECIST 1.1<br /><br>- Duration of response<br /><br>- Time to progression (for TGCT and other non-malignant tumors)<br /><br>- Progression-free survival (for malignant tumors)<br /><br><br /><br>Safety<br /><br>- TEAEs<br /><br>- Vital signs<br /><br>- Electrocardiograms (ECGs)<br /><br>- Clinical laboratory tests including AST/ALT/Total bilirubin (TBil)<br /><br><br /><br>Exploratory Endpoints<br /><br>- PGx biomarkers<br /><br>- Optional: PDy biomarkers<br /><br>- Optional: Tumor biomarker analysis</p><br>