Purpose

The purpose of this study is to determine the safety of TAS-119 and determine the most appropriate dose in combination with Paclitaxel for subsequent studies in patients with advanced solid tumors. TAS-119 is a novel, selective Aurora A kinase inhibitor, which has previously been demonstrated to enhance the activity of paclitaxel in preclinical studies

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Is a male or female ≥ 18 years of age, that has provided written informed consent. 2. Has histologically or cytologically confirmed advanced, unresectable metastatic solid tumor(s) for which the patients have no available therapy likely to provide clinical benefit, or for which paclitaxel is considered a standard of care. 3. Has adequate organ function as defined by the following criteria: - Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5 × ULN. - Total serum bilirubin ≤ 1.5 × ULN. - Absolute neutrophil count ≥ 1,500/mm3 (excluding measurements obtained within 7 days after administration of granulocyte colony-stimulating factor [G-CSF]). - Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L) (excluding measurements obtained within 7 days after a transfusion of platelets). - Hemoglobin ≥ 9.0 g/dL - Total serum creatinine ≤ 1.5 × ULN - Serum albumin ≥ 3.0 mg/dL.

Exclusion Criteria

  1. Previous inability to tolerate any dose of paclitaxel (i.e., the subject required a paclitaxel dose reduction or discontinuation). 2. Has received any treatments prohibited in this trial within specified time frames 3. Has a serious illness or medical condition(s) that would affect safety or tolerability of the study treatments 4. Has history of Grade 2 or greater peripheral neuropathy during the 3 months prior to enrollment. 5. Has known hypersensitivity to TAS-119 or its components. 6. Has known hypersensitivity to Cremophor® EL, paclitaxel or its components. 7. Is a pregnant or lactating female.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
TAS-119
TAS-119 tablets, oral, dose-escalating, 28-day cycle. Paclitaxel (90mg/m2) is administered IV in combination with TAS-119 in each of the arms.
  • Drug: TAS-119
  • Drug: Paclitaxel
    A dose of 90 mg/m2 is used in combination with various doses of TAS-119.
    Other names:
    • Taxol

More Details

Status
Terminated
Sponsor
Taiho Oncology, Inc.

Study Contact

Detailed Description

Background and rationale for study: In nonclinical pharmacology studies TAS-119 significantly enhanced the antitumor activity of the microtubule stabilizer paclitaxel and TAS-119 is being developed for use in combination with paclitaxel. TAS-119 selectively inhibits the kinase inhibitor Aurora A. AurA regulates cell division by controlling the transition from G2 to M phase. Overexpression of AurA is associated with resistance to taxanes. The study will be conducted in two sequential phases: Dose Escalation Phase with the purpose to determine the maximum tolerated dose and the recommended Phase 2 dose of TAS-119 given in combination with paclitaxel An Expansion Phase in which additional patients will be enrolled to further evaluate the safety and preliminary efficacy of the recommended Phase 2 dose of TAS-119 in combination with paclitaxel, during which a subgroup of patients will be evaluated for DDI between paclitaxel and TAS-119 via PK assessment.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.