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Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02734433
Recruitment Status : Active, not recruiting
First Posted : April 12, 2016
Results First Posted : April 24, 2020
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: Pexidartinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Single Agent Pexidartinib in Asian Subjects With Advanced Solid Tumors
Actual Study Start Date : June 2016
Actual Primary Completion Date : June 13, 2017
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
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.
Drug: Pexidartinib



Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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) ]
  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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 ]
  13. Number and Percentage of Participants With Treatment-related TEAEs by Preferred Term (Safety Analysis Set) [ Time Frame: Baseline up to 18 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734433


Locations
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Taiwan
Taipei, Taiwan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02734433    
Other Study ID Numbers: PL3397-A-A103
First Posted: April 12, 2016    Key Record Dates
Results First Posted: April 24, 2020
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/

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Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Advanced solid tumors
Asian subjects
Developmental Phase I
Additional relevant MeSH terms:
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Neoplasms