Clinical trial NCT02734433: Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors
Official title: A Phase 1 Study of Single Agent Pexidartinib in Asian Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced solid tumors
Asian subjects
Developmental Phase I
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2016-04-12
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Major surgery: ≥ 4 weeks (2 weeks for less invasive surgery, such as colostomy)
  2. Radiation therapy (eg, whole brain radiotherapy): ≥ 4 weeks (if palliative stereotactic radiation therapy, ≥ 2 weeks)
  3. 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)
  4. Other investigational drug therapy: ≥ 4 weeks

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall Response Based on RECIST V1.1 Following Oral Doses of Pexidartinib (Efficacy Analysis Set)
timeFrame: Day 1 through Day 28 after last dose (within 18 months)
Secondary outcomes:
measure: Duration of Response or Duration of Stable Disease Following Oral Doses of Pexidartinib (Efficacy Analysis Set)
timeFrame: Day 1 through Day 28 after last dose (within 18 months)
measure: A Summary of Pexidartinib Pharmacokinetic Parameter (Cmax) by Cohort and Day Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Pexidartinib Pharmacokinetic Parameter (AUC[0-8h]) by Cohort and Day Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Pexidartinib Pharmacokinetic Parameter (Tmax) by Cohort and Day Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Pexidartinib Pharmacokinetic Parameter (R[AUC]) by Cohort Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Pexidartinib Pharmacokinetic Parameter (R[Cmax]) by Cohort Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (AUC[0-8h]) Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Cmax) Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (Tmax) Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR AUC[0-8h]) Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: A Summary of Plasma ZAAD-1006a Pharmacokinetic Parameter (MR Cmax) Following Oral Doses of Pexidartinib
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5h, 1h, 2h, 4h, and 8h postdose (each cycle was 28 days)
measure: Number and Percentage of Participants With Common Treatment-emergent Adverse Events (TEAEs) (≥20%) Classified by Preferred Term (Safety Analysis Set)
timeFrame: Baseline through study completion, up to 18 months
measure: Number and Percentage of Participants With Treatment-related TEAEs by Preferred Term (Safety Analysis Set)
timeFrame: Baseline through study completion, up to 18 months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.