Dose-escalating, Safety, Tolerability and PK Study of TAS-119 in Combination With Paclitaxel in Patients With Advanced Solid Tumors

NCT ID: NCT02134067

Last Updated: 2024-09-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2018-07-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Advanced Solid Tumors

Keywords

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advanced solid tumors tumor Dose Escalation TAS-119 Taxane Paclitaxel Aurora A kinase inhibitor AurA

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

TAS-119

Intervention Type DRUG

Paclitaxel

Intervention Type DRUG

A dose of 90 mg/m2 is used in combination with various doses of TAS-119.

Interventions

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TAS-119

Intervention Type DRUG

Paclitaxel

A dose of 90 mg/m2 is used in combination with various doses of TAS-119.

Intervention Type DRUG

Other Intervention Names

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Taxol

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Washington University School of Medicine Division of Oncology Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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TO-TAS-119-101

Identifier Type: -

Identifier Source: org_study_id