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Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02734433
Recruitment Status : Active, not recruiting
First Posted : April 12, 2016
Results First Posted : April 24, 2020
Last Update Posted : November 9, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Tracking Information
First Submitted Date  ICMJE March 22, 2016
First Posted Date  ICMJE April 12, 2016
Results First Submitted Date  ICMJE March 23, 2020
Results First Posted Date  ICMJE April 24, 2020
Last Update Posted Date November 9, 2020
Actual Study Start Date  ICMJE June 2016
Actual Primary Completion Date June 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 5, 2016)
  • Number and severity of adverse events [ Time Frame: day 1 through day 28 after last dose ]
  • Number and severity of laboratory abnormalities [ Time Frame: day 1 through day 28 after last dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2016)
  • Maximum concentration (Cmax) [ Time Frame: day 28 ]
  • Time of maximum concentration (Tmax) [ Time Frame: day 28 ]
  • Area under plasma-concentration curve (AUC) [ Time Frame: day 28 ]
  • Level of macrophage colony stimulating factor (CSF-1) [ Time Frame: day 28 ]
  • Level of Adiponectin [ Time Frame: day 28 ]
  • Tumor response by radiological scan [ Time Frame: week 8, 16, 24, 32 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Study of Single Agent Pexidartinib in Asian Subjects With Advanced Solid Tumors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: Pexidartinib
Study Arms  ICMJE 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.
Intervention: Drug: Pexidartinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 22, 2020)
12
Original Estimated Enrollment  ICMJE
 (submitted: April 5, 2016)
15
Estimated Study Completion Date  ICMJE August 2021
Actual Primary Completion Date June 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02734433
Other Study ID Numbers  ICMJE PL3397-A-A103
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
Study Sponsor  ICMJE Daiichi Sankyo Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP