Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors

Overview

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.

Full Title of Study: “A Phase 1 Study of Single Agent Pexidartinib in Asian Subjects With Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 13, 2017

Interventions

  • Drug: Pexidartinib

Arms, Groups and Cohorts

  • Experimental: Pexidartinib
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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)
    • 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.

Secondary Measures

  • 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)
  • 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
    • Maximum concentration (Cmax) of pexidartinib was assessed.
  • 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
    • Area under the curve from 0 to 8 hours (AUC[0-8h]) was assessed.
  • 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
    • Time at maximum pexidartinib concentration (Tmax) was assessed.
  • 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
    • Accumulation ratio of area under the curve (R[AUC]) was assessed.
  • 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
    • Accumulation ratio of maximum concentration of pexidartinib (R[Cmax]) was assessed.
  • 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
    • Area under the curve from 0 to 8 hours (AUC[0-8h]) was assessed.
  • 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
    • Maximum concentration (Cmax) of pexidartinib was assessed.
  • 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
    • Time at maximum pexidartinib concentration (Tmax) was assessed.
  • 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
    • Metabolite to parent drug ratio of area under the curve from 0-8 h (MR AUC[0-8h]) was assessed.
  • 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
    • Metabolite to parent drug ratio of maximum pexidartinib concentration (MR Cmax) was assessed.
  • 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
  • Number and Percentage of Participants With Treatment-related TEAEs by Preferred Term (Safety Analysis Set)
    • Time Frame: Baseline up to 18 months

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Daiichi Sankyo Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Global Clinical Leader, Study Director, Daiichi Sankyo, Inc.

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