Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

NCT ID: NCT03291288

Last Updated: 2021-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-26
• Study Completion Date: 2021-04-16

Brief Summary

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.

Conditions

Drug Interaction Potential

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pexidartinib

Part 1 (Drug-drug Interaction Phase):

On Day 1, all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/d) in twice daily (400 mg BID) dosing will be initiated and continue throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning dose of pexidartinib (400 mg).

Part 2 (Efficacy and Safety Phase):

All participants will continue to receive pexidartinib 400 mg BID.

Group Type: EXPERIMENTAL

Tolbutamide

Intervention Type: DRUG

Commercially available tolbutamide

Midazolam

Intervention Type: DRUG

Commercially available midazolam

Pexidartinib

Intervention Type: DRUG

Pexidartinib is formulated as opaque, white, 200-mg capsules

Interventions

Tolbutamide

Commercially available tolbutamide

Intervention Type: DRUG

Midazolam

Commercially available midazolam

Intervention Type: DRUG

Pexidartinib

Pexidartinib is formulated as opaque, white, 200-mg capsules

Intervention Type: DRUG

Other Intervention Names

Orinase; Dormicum; Hypnovel; Versed; Others; PLX-3397

Eligibility Criteria

Inclusion Criteria

• Is the age of majority in country of residence
• Has a diagnosis of:

1. tenosynovial 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)

2. KIT-mutant tumor, including melanoma or gastrointestinal stromal tumor (GIST), for which there is no standard systemic therapy, or

3. other 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

• If a female of childbearing potential, had a negative serum pregnancy test within 14 days before enrollment, or within 72 hours before enrollment where required
• Is a non-sterile male or female willing to use of one of the protocol-defined highly effective contraception methods:

1. intra-uterine device (nonhormonal or hormonal)

2. sexual abstinence (only if this is in line with the patient's current lifestyle)

3. barrier methods (eg, condom, diaphragm) used in combination with hormonal methods associated with inhibition of ovulation

• Is a surgically sterile male or female, or is postmenopausal for at least 1 year, at least 50 years of age, with a follicle-stimulating hormone level > 40 milli-International units per mL (mIU/mL)
• Has adequate hematologic, hepatic, and renal function as defined by the protocol
• Is able and willing to follow all study procedures
• Has provided a signed informed consent

Exclusion Criteria

• Is pregnant or breastfeeding
• Is unable to swallow oral medication
• Is unable to follow study procedures
• Is taking or has taken any medications or therapies outside of protocol-defined parameters
• Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:

1. safety and well-being of the participant or offspring

2. safety of study staff

3. analysis of results

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_CHAIR

Daiichi Sankyo

Locations

HonorHealth

Scottsdale, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Stanford University

Palo Alto, California, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Northwell Health

Lake Success, New York, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Christchurch Hospital NZ

Christchurch, , New Zealand

National Taiwan University Hospital

Taipei, , Taiwan

Countries

United States; Netherlands; New Zealand; Taiwan

References

Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24.

Reference Type: DERIVED

PMID: 33289960 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PL3397-A-U126

Identifier Type: -

Identifier Source: org_study_id