Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors

NCT02734433 | Completed Phase 1 Results

• 1 other identifier: PL3397-A-A103
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, non-randomized, open-label, multiple dose study of pexidartinib in Asian subjects with advanced solid tumors. The study will be conducted in a dose escalation to assess the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary antitumor activity of pexidartinib.

Conditions

Advanced Solid Tumors

Keywords

Advanced solid tumors; Asian subjects; Developmental Phase I

Outcome Measures

Primary Outcomes (1)

• Overall Response Based on RECIST V1.1 Following Oral Doses of Pexidartinib (Efficacy Analysis Set)

  For the assessment of tumor response, participants were classified into the best of the following tumor response categories by RECIST v1.1: complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease (SD); neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm; or not evaluable (NE) for analysis. Objective response rate was defined as CR or PR and disease control rate was defined as CR, PR, or SD.

  Day 1 through Day 28 after last dose (within 18 months)

Secondary Outcomes (13)

• Duration of Response or Duration of Stable Disease Following Oral Doses of Pexidartinib (Efficacy Analysis Set)

  Day 1 through Day 28 after last dose (within 18 months)

• A Summary of Pexidartinib Pharmacokinetic Parameter (Cmax) by Cohort and Day Following Oral Doses of Pexidartinib

  Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)

• A Summary of Pexidartinib Pharmacokinetic Parameter (AUC[0-8h]) by Cohort and Day Following Oral Doses of Pexidartinib

  Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)

• A Summary of Pexidartinib Pharmacokinetic Parameter (Tmax) by Cohort and Day Following Oral Doses of Pexidartinib

  Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)

• A Summary of Pexidartinib Pharmacokinetic Parameter (R[AUC]) by Cohort Following Oral Doses of Pexidartinib

  Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)

Study Arms (1)

Pexidartinib

EXPERIMENTAL

Pexidartinib capsules administered twice daily in the morning and evening. Each cycle of treatment is 28 days in duration. The cycle of treatment is continued until disease progression, unacceptable toxicity, or consent withdrawal.

Drug: Pexidartinib

Interventions

Pexidartinib DRUG

Pexidartinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age should be ≥ 20 years
• 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
• All associated toxicity from previous cancer therapy must have been resolved (to ≤ Grade 1) prior to administration of pexidartinib
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Adequate hematologic, hepatic, and renal function tests
• 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

You may not qualify if:

• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would have precluded adequate absorption
• 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
• 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
• Active or chronic infection with hepatitis C or known positive hepatitis B surface. antigen, or known active or chronic infection with human immunodeficiency virus
• A screening Fridericia-corrected time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QTcF) ≥ 450 ms (in men) or ≥ 470 ms (in women).
• A medical history or complications of clinically significant lung disease (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis)
• A history of symptomatic congestive heart failure (CHF) \[New York Heart Association (NYHA) Classes II to IV\] or serious cardiac arrhythmia requiring treatment
• A history of myocardial infarction or unstable angina within 6 months before enrollment
• An uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead

Study Sites (1)

Unknown Facility

Taipei, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 33289960 DERIVED

• Lee JH, Chen TW, Hsu CH, Yen YH, Yang JC, Cheng AL, Sasaki SI, Chiu LL, Sugihara M, Ishizuka T, Oguma T, Tajima N, Lin CC. A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors. Invest New Drugs. 2020 Feb;38(1):99-110. doi: 10.1007/s10637-019-00745-z. Epub 2019 Mar 2.

  PMID: 30825104 DERIVED

MeSH Terms

Interventions

pexidartinib

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: April 12, 2016
• Study Start: June 1, 2016
• Primary Completion: June 13, 2017
• Study Completion: May 28, 2021
• Last Updated: April 25, 2022
• Results First Posted: April 24, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)