An Open-Label, Dose-Escalation/Expansion Phase 1 Study of ASP4132 Given Orally to Patients With Advanced Refractory Solid Tumors and Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- ASP4132
- Conditions
- Lymphoma
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 39
- Locations
- 5
- Primary Endpoint
- Safety as assessed by electrocardiograms (ECG)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of ASP4132 and to determine the maximum tolerated dose and recommended phase 2 dose of ASP4132. The study will also determine the pharmacokinetics (PK) of ASP4132 and evaluate the preliminary antitumor activity.
Detailed Description
The study consists of two parts and these will be conducted sequentially: Part 1 (dose escalation) and Part 2 (dose expansion). Subjects will participate in Part 1 or Part 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has a life expectancy of more than 3 months
- •Subject agrees not to participate in another interventional study while on treatment.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Female subject must be either:
- •Of non-child bearing potential:
- •post-menopausal (defined as at least 1 year without any menses) prior to Screening,
- •or, documented surgically sterile or status post hysterectomy
- •Or, if of childbearing potential,
- •agree not to try to become pregnant during the study and for 90 days after the final study drug administration;
- •if heterosexually active must use two forms of birth control
Exclusion Criteria
- •Subject has absolute neutrophil count \< 1000/μL, platelet count \< 75,000/μL, and hemoglobin \< 8 g/dL (\< 5 mmol/L) at Screening
- •Subject has total serum bilirubin ≥1.5 times the upper limit of normal (ULN),serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) \> 3 times ULN, or albumin ≤ 3.0 g/dL at Screening.
- •Subject has any abnormalities in serum sodium, potassium, chloride, calcium and magnesium levels ≥ Grade 2 at screening (CTCAE Version 4.03).
- •Subject has a known elevation in serum lactate at screening ˃ 2x institutional ULN
- •Subject has an estimated glomerular filtration rate (eGFr) of \< 60ml/min as calculated by the modification of diet Renal disease (MDRD) Equation.
- •Subject with a QTcF of \> 450 msec in male subjects and \> 470 msec in female subjects on the screening 12 lead ECG.
- •Subject has Neuropathy ≥ Grade 2 at Screening.
- •Subject has Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus and currently being treated with insulin or sulfonylureas.
- •Subject has concomitant active second malignancies unless remission was achieved at least 3 years prior to study entry and subject is no longer on therapy for the malignancy.
- •Subject has a significant cardiovascular disease
Arms & Interventions
ASP4132 dose escalation
Subjects will receive a single dose of the study drug on Day -4 (Single-Dose Period), followed by PK sampling prior to Multiple-Dose Period where they will receive the same dose as they received in the Single-Dose Period on one of four schedules: Continuous - daily dosing for 28 days, Intermittent: Schedule A: 3 days on / 4 days off; Schedule B: 1 days on / 6 days off; Schedule C: 3 days on / 11 days off.
Intervention: ASP4132
ASP4132 dose expansion
Subjects in Part 2 will be treated with ASP4132 at the MTD and dosing schedule identified from Part 1.
Intervention: ASP4132
Outcomes
Primary Outcomes
Safety as assessed by electrocardiograms (ECG)
Time Frame: up to 39 months
Safety as assessed by adverse events
Time Frame: up to 39 months
Safety as assessed by clinical laboratory tests
Time Frame: up to 39 months
Safety as assessed by vital signs
Time Frame: up to 39 months
Secondary Outcomes
- Objective response rate to ASP4132(Week 16)
- Duration of response to ASP4132(Week 16)
- Disease control rate to ASP4132(Week 16)
- Maximum concentration (Cmax) of ASP4132(up to 43 days)
- Time of the maximum concentration (Tmax) of ASP4132(up to 43 days)
- Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of ASP4132(up to 43 days)
- AUC from the time of dosing to 24 hours (AUC24) of ASP4132(up to 43 days)
- AUC from the time of dosing extrapolated to time infinity (AUCinf) of ASP4132(up to 43 days)
- Apparent terminal elimination half-life (T1/2) of ASP4132(up to 43 days)
- Accumulation ratio of ASP4132(up to 43 days)
- Apparent total systemic clearance after single or multiple extravascular dosing (CL/F) of ASP4132(up to 43 days)
- Apparent volume of distribution during the terminal elimination phase after single or multiple extravascular dosing (Vz/F) of ASP4132(up to 43 days)
- Progression-free survival(up to 39 months)