Details

Details

Title A Phase 1 Open-label Study to Investigate the Absorption, Metabolism and Excretion of [14C]-ASP2215 in Patients with Advanced Solid Tumors

IRB APGD1Y15

CC 15-1307

Hospital Main Campus

Phase Phase 1

Disease Solid Tumors

Drug ASP2215

Description

Description

Primary Objective
  • To evaluate the pharmacokinetics of [14C]-ASP2215, in particular, the routes of excretion and extent of metabolism of ASP2215 following administration of a single dose of [14C]-ASP2215 after repeated doses of ASP2215 tablets
Secondary Objectives
  • To evaluate the safety of repeated oral administration of ASP2215 in subjects with advanced solid tumors
  • To identify the metabolic profile of ASP2215 in plasma, urine and feces after a single oral dose of [14C]-ASP2215
Inclusion Criteria

Inclusion Criteria

  1. Subject must sign an Institutional Review Board (IRB)-approved written Informed Consent and Health Insurance Portability and Accountability Act [HIPAA] authorization prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
  2. Subject is male or female ≥ 18 years of age.
  3. Subject had histologically or cytologically confirmed diagnosis of advanced solid tumor (measurable or nonmeasurable disease) for which no standard therapy is available.
  4. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  5. Subject must have a life expectancy > 12 weeks.
  6. Subject must have recovered from the effects of prior systemic antineoplastic or radiation therapy(s) to ≤ Grade 1 (National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 4.03) severity or to subject's baseline values, excluding alopecia.
  7. Subject has adequate bone marrow, renal and hepatic function at baseline, as demonstrated by the following:
    • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
    • Platelet count ≥ 100,000 cells/mm3
    • Hemoglobin (Hb) ≥ 9 g/dL
    • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance > 60 mL/min if the serum creatinine is > 1.5 x ULN
    • Total bilirubin (TBL) ≤ 1.5 x ULN
    • AST or ALT ≤ 3 x ULN (or < 5 x ULN in subjects with liver metastases or hepatocellular carcinoma).
  8. Female subject must either:
    • Be of nonchildbearing potential:
      • postmenopausal (defined as at least 1 year without any menses) prior to screening, or
      • documented surgically sterile
    • Or, if of childbearing potential:
      • agree not to try to become pregnant during the study and for 60 days after the final study drug administration
      • and have a negative serum or urine pregnancy test at screening, and
      • if heterosexually active, agree to consistently use 2 forms of birth control (at least one of which must be a barrier method) starting at screening and throughout the study period and for 60 days after final study drug administration.
  9. Female subject must not be breastfeeding at screening or during the study period, and for 60 days after the final study drug administration.
  10. Female subject must not donate ova starting at screening and throughout the study period and for 60 days after final study drug administration.
  11. Male subject and a female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (one of which must be a barrier method) starting at screening and continue throughout the study period and for 120 days after the final study drug administration
  12. Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after final study drug administration.
  13. Subject must be willing to comply with all procedures and assessments.

NOTE: 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

Exclusion Criteria

  1. Subject has received more than 5 prior cytotoxic agent-containing regimens.
  2. Subject has symptomatic CNS metastases or leptomeningeal involvement as assessed through medical history review and physical examination. Subject with prior brain metastases must:
    • have stable neurologic status post administration of local therapy (surgery or radiation) for a minimum of 2 weeks following completion of the definitive therapy.
    • be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  3. Subject has had major surgery within 4 weeks prior to the first study dose.
  4. Subject has had chemotherapy within 4 weeks prior to the first study dose.
  5. Subject has had radiation therapy within 4 weeks prior to the first study dose.
  6. Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or suspected active hepatitis C infection; or known human immunodeficiency virus (HIV) positive.
  7. Subject with malabsorption syndrome or disease or condition significantly affecting gastrointestinal function.
  8. Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic disorders or significant psychological conditions at baseline that in the investigator's opinion, makes the subject unsuitable for study participation.
  9. Subject with ECG abnormalities on a12-lead ECG performed within 14 days before start of the study drug that are considered by the investigator to be clinically significant.
  10. Subject who requires treatment with concomitant drugs that are strong inducers of CYP3A.
  11. Subject who has received strong or moderate CYP3A4 inhibitors (e.g., ketoconazole or fluconazole), or strong inhibitors or inducers of P-gp, or substrates of MATE1 with the exception of antibiotics, antifungals, and antivirals that are used to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject within 2 weeks prior to start of study treatment and while on study.
  12. Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the subject.
  13. Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to the initiation of screening.
  14. Subject has a known history of serious hypersensitivity to ASP2215, or any component of the formulation used.
  15. Subject who 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.
  16. Subject has had any of the following within 14 days prior to the first dose of study drug:
    • blood transfusion or hematopoietic factor therapy
    • evidence of active infection requiring systemic therapy.
  17. Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
  18. Subject with mean Fridericia-corrected QT interval (QTcF) > 450 ms at screening based on central reading.
  19. Subject with long corrected QT interval (QTc) syndrome at screening.
  20. Subject with hypokalemia and hypomagnesemia at screening (defined as values below lower limit of normal [LLN]).