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A Study to Investigate the Absorption, Metabolism and Excretion of [14C]ASP8273 in Subjects With Solid Tumors

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ClinicalTrials.gov Identifier: NCT02674555
Recruitment Status : Withdrawn (Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.)
First Posted : February 4, 2016
Last Update Posted : July 28, 2017
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
This is a study to investigate the absorption, metabolism and excretion of [14C] labeled ASP8273 in subjects with solid tumors harboring EGFR mutations (per local testing). This study consists of two parts (A and B).

Condition or disease Intervention/treatment Phase
Epidermal Growth Factor Receptor (EGFR) Mutations Solid Tumors Drug: radio-labeled naquotinib Drug: naquotinib Phase 1

Detailed Description:

This study consists of two parts (A and B).

In Part A, eligible subjects will be admitted to the site on day -1 and remain confined at the site until postdosing discharge criteria are met. Subjects will receive a single dose of [14C] ASP8273 solution on study day 1.

Once Part A has been completed, subjects may elect to continue participation in Part B. Subjects will receive oral administration of ASP8273 (nonradiolabeled) once daily in 28-day cycles.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C]ASP8273 in Subjects With Solid Tumors Harboring Epidermal Growth Factor Receptor (EGFR) Mutations
Actual Study Start Date : November 15, 2016
Actual Primary Completion Date : November 15, 2016
Actual Study Completion Date : November 15, 2016

Arm Intervention/treatment
Experimental: ASP8273
Two Parts - Part A: 14C-radio labeled; Part B: non radio labeled (optional)
Drug: radio-labeled naquotinib
Oral administration
Other Name: ASP8273

Drug: naquotinib
Oral administration
Other Name: ASP8273




Primary Outcome Measures :
  1. Part A: Radioactivity in whole blood: AUCinf [ Time Frame: Up to 14 days ]
    AUCinf: area under the concentration-time curve from the time of dosing extrapolated to time infinity

  2. Part A: Radioactivity in whole blood: AUClast [ Time Frame: Up to 14 days ]
    AUClast: area under the concentration-time curve from the time of dosing to the last measurable concentration

  3. Part A: Radioactivity in whole blood: Cmax [ Time Frame: Up to 14 days ]
    Cmax: maximum concentration

  4. Part A: Radioactivity in whole blood: tmax [ Time Frame: Up to 14 days ]
    tmax: time to maximum concentration

  5. Part A: Radioactivity in whole blood: t1/2 [ Time Frame: Up to 14 days ]
    t1/2: apparent terminal elimination half-life

  6. Part A: Radioactivity in plasma: AUCinf [ Time Frame: Up to 14 days ]
  7. Part A: Radioactivity in plasma: AUClast [ Time Frame: Up to 14 days ]
  8. Part A: Radioactivity in plasma: Cmax [ Time Frame: Up to 14 days ]
  9. Part A: Radioactivity in plasma: tmax [ Time Frame: Up to 14 days ]
  10. Part A: Radioactivity in plasma: t1/2 [ Time Frame: Up to 14 days ]
  11. Part A: Radioactivity ratio for whole blood/plasma concentration (per time point.) [ Time Frame: Up to 14 days ]
  12. Part A: Radioactivity ratio for whole blood/plasma AUCinf [ Time Frame: Up to 14 days ]
  13. Part A: Radioactivity ratio for whole blood/plasma AUClast [ Time Frame: Up to 14 days ]
  14. Part A: Excretion ratio of radioactivity in urine [ Time Frame: Up to 14 days ]
  15. Part A: Cumulative excretion of radioactivity in urine [ Time Frame: Up to 14 days ]
  16. Part A: Excretion ratio of radioactivity in feces [ Time Frame: Up to 14 days ]
  17. Part A: Cumulative excretion of radioactivity in feces [ Time Frame: Up to 14 days ]
  18. Part A: Total excretion ratio of radioactivity in urine and feces [ Time Frame: Up to 14 days ]
  19. Part A: Total cumulative excretion of radioactivity in urine and feces [ Time Frame: Up to 14 days ]
  20. Part A: Radioactivity in emesis (if applicable) [ Time Frame: Up to 14 days ]
  21. Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: AUCinf [ Time Frame: Up to 14 days ]
  22. Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: AUClast [ Time Frame: Up to 14 days ]
  23. Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: Cmax [ Time Frame: Up to 14 days ]
  24. Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: tmax [ Time Frame: Up to 14 days ]
  25. Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: t1/2 [ Time Frame: Up to 14 days ]
  26. Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine: (Aelast) [ Time Frame: Up to 14 days ]
    Aelast: cumulative amount of drug excreted from time of dosing up to the collection time of the last measurable concentration

  27. Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine CLr [ Time Frame: Up to 14 days ]
    CLr: renal clearance

  28. Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine: % of dose excreted (Aelast%) [ Time Frame: Up to 14 days ]

Secondary Outcome Measures :
  1. Part A: Profiling of possible metabolites of ASP8273 in plasma [ Time Frame: Up to 14 days ]
    Identification and possible quantification of metabolites in plasma

  2. Part A: Profiling of possible metabolites of ASP8273 in urine [ Time Frame: Up to 14 days ]
    Identification and possible quantification of metabolites in urine

  3. Part A: Profiling of possible metabolites of ASP8273 in feces [ Time Frame: Up to 14 days ]
    Identification and possible quantification of metabolites in feces

  4. Part A and Part B: Safety profile assessed by adverse event reporting, vital signs, electrocardiograms (ECG), clinical laboratory tests, and physical examinations [ Time Frame: Up to 36 months ]
    Vital signs include oral temperature, pulse, and blood pressure. Clinical laboratory evaluations include hematology, chemistry and urinalysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has histologically or cytologically confirmed metastatic or locally advanced, unresectable solid tumors harboring EGFR mutations.
  • Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Subject must meet all of the following criteria on the laboratory tests that will be performed within 7 days prior to enrollment. In case of multiple laboratory data within this period, the most recent data should be used.

    • Neutrophil count ≥ 1,000/mm3
    • Platelet count ≥ 7.5 × 104/mm3
    • Hemoglobin ≥ 9.0 g/dL
    • Lymphocyte count ≥ 500/mm3
    • Estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Cockcroft-Gault Method
    • Total bilirubin (TBL) < 1.5 × upper limit of normal (ULN; except for subjects with documented Gilbert's syndrome)
    • Aspartate aminotransferase (AST) and ALT < 3.0 × ULN
    • Serum sodium level is ≥ 130 mmol/L
  • Female subject must either be:

    • Of nonchild bearing potential:

      1. Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
      2. Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening).
    • Or, if of childbearing potential:

      1. Agree not to try to become pregnant during the study and for 28 days after the final study drug administration,
      2. Must have a negative serum pregnancy test at screening and day -1, and
      3. If heterosexually active must use two forms of birth control* (at least one of which must be a barrier method) starting at screening and throughout the study period and for 28 days after the final study drug administration.
  • Female subject must not be breastfeeding at screening or during the study period, and for 28 days after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
  • Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of two forms of birth control* (one of which must be a barrier method) starting at screening and continue throughout the study period and for 90 days after the final study drug administration.
  • Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.

    *Acceptable forms of birth control include:

  • Established use of oral, injected or implanted hormonal methods of contraception.
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

Exclusion Criteria:

  • Subject has an ongoing toxicity ≥ Grade 2 (Common Terminology Criteria for Adverse Event [CTCAE] v4.03) attributable to prior medication to treat solid tumor (except alopecia) at the time of screening.
  • Subject has known history of serious hypersensitivity reaction to ASP8273, or any component of the formulation used.
  • Subject has received investigational therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study drug.
  • Subject has received a prior EGFR inhibitor within 6 days prior to the first dose of study drug.
  • Subject has had any of the following within 14 days prior to the first dose of study drug:

    • A treatment with any other agent with antitumor activity including chemotherapy, radiotherapy, or immunotherapy
    • A major surgical procedure (other than study related biopsy), or a major surgical is planned to occur during the study
    • Blood transfusions or hemopoietic factor therapy
    • Evidence of active infection requiring systemic therapy
  • Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 1 week prior the first dose of study drug.
  • Subject has ≥ CTCAE v4.03 Grade 2 neuropathy.
  • Subject has a known history of a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV).
  • Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
  • Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
  • Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
  • Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any grade.
  • Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
  • Subject has history of severe/unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to the first dose of study drug.
  • Subject has concurrent corneal disorder or any ophthalmologic condition which, in the Investigator's opinion, makes the subject unsuitable for study participation (e.g., advanced cataracts, glaucoma, or subject is unable to undergo a comprehensive ophthalmologic exam).
  • Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the first dose of study drug.
  • Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
  • Subject who has received strong/moderate inhibitors or inducers of CYP3A4 within 14 days prior to the first dose of study drug.

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): NCT02674555


Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
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Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02674555    
Other Study ID Numbers: 8273-CL-0104
First Posted: February 4, 2016    Key Record Dates
Last Update Posted: July 28, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Phase 1
Metabolism
Excretion
Absorption
[14C]-radioactivity
Pharmacokinetics
naquotinib
Oncology
Additional relevant MeSH terms:
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Neoplasms
Naquotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action