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

NCT02674555 | Withdrawn Phase 1

• 1 other identifier: 8273-CL-0104
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Epidermal Growth Factor Receptor (EGFR) Mutations; Solid Tumors

Keywords

Phase 1; Metabolism; Excretion; Absorption; [14C]-radioactivity; Pharmacokinetics; naquotinib; Oncology

Outcome Measures

Primary Outcomes (28)

• Part A: Radioactivity in whole blood: AUCinf

  AUCinf: area under the concentration-time curve from the time of dosing extrapolated to time infinity

  Up to 14 days

• Part A: Radioactivity in whole blood: AUClast

  AUClast: area under the concentration-time curve from the time of dosing to the last measurable concentration

  Up to 14 days

• Part A: Radioactivity in whole blood: Cmax

  Cmax: maximum concentration

  Up to 14 days

• Part A: Radioactivity in whole blood: tmax

  tmax: time to maximum concentration

  Up to 14 days

• Part A: Radioactivity in whole blood: t1/2

  t1/2: apparent terminal elimination half-life

  Up to 14 days

• Part A: Radioactivity in plasma: AUCinf

  Up to 14 days

• Part A: Radioactivity in plasma: AUClast

  Up to 14 days

• Part A: Radioactivity in plasma: Cmax

  Up to 14 days

• Part A: Radioactivity in plasma: tmax

  Up to 14 days

• Part A: Radioactivity in plasma: t1/2

  Up to 14 days

• Part A: Radioactivity ratio for whole blood/plasma concentration (per time point.)

  Up to 14 days

• Part A: Radioactivity ratio for whole blood/plasma AUCinf

  Up to 14 days

• Part A: Radioactivity ratio for whole blood/plasma AUClast

  Up to 14 days

• Part A: Excretion ratio of radioactivity in urine

  Up to 14 days

• Part A: Cumulative excretion of radioactivity in urine

  Up to 14 days

• Part A: Excretion ratio of radioactivity in feces

  Up to 14 days

• Part A: Cumulative excretion of radioactivity in feces

  Up to 14 days

• Part A: Total excretion ratio of radioactivity in urine and feces

  Up to 14 days

• Part A: Total cumulative excretion of radioactivity in urine and feces

  Up to 14 days

• Part A: Radioactivity in emesis (if applicable)

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: AUCinf

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: AUClast

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: Cmax

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: tmax

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in plasma: t1/2

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine: (Aelast)

  Aelast: cumulative amount of drug excreted from time of dosing up to the collection time of the last measurable concentration

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine CLr

  CLr: renal clearance

  Up to 14 days

• Part A: Pharmacokinetics of ASP8273 and possible metabolites in urine: % of dose excreted (Aelast%)

  Up to 14 days

Secondary Outcomes (4)

• Part A: Profiling of possible metabolites of ASP8273 in plasma

  Up to 14 days

• Part A: Profiling of possible metabolites of ASP8273 in urine

  Up to 14 days

• Part A: Profiling of possible metabolites of ASP8273 in feces

  Up to 14 days

• Part A and Part B: Safety profile assessed by adverse event reporting, vital signs, electrocardiograms (ECG), clinical laboratory tests, and physical examinations

  Up to 36 months

Study Arms (1)

ASP8273

EXPERIMENTAL

Two Parts - Part A: 14C-radio labeled; Part B: non radio labeled (optional)

Drug: radio-labeled naquotinib; Drug: naquotinib

Interventions

radio-labeled naquotinib DRUG

Oral administration

Also known as: ASP8273

ASP8273

naquotinib DRUG

Oral administration

Also known as: ASP8273

ASP8273

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

MeSH Terms

Conditions

Neoplasms

Interventions

naquotinib

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 4, 2016
• Study Start: November 15, 2016
• Primary Completion: November 15, 2016
• Study Completion: November 15, 2016
• Last Updated: July 28, 2017

Record last verified: 2017-07