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

NCT02134067 | Terminated Phase 1

• 1 other identifier: TO-TAS-119-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Advanced Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of TAS-119 in combination with paclitaxel

  Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 will be used. The safety and tolerability of TAS-119 will be evaluated by the number and severity of adverse events, vital signs, physical exam, and clinical laboratory assessments.

  Safety monitoring will begin at the time of the first dose of TAS-119, and will continue until all patients are discontinued from treatment or until 12 months from the last patient enrolled (up to 3 years).

Secondary Outcomes (1)

• Overall response according to RECIST guidelines (version 1.1, 2009)

  Computed tomography (CT) scans for tumor imaging will be performed at the end of every 2 treatment cycles (8 weeks) and an average of 4 cycles (16 weeks)

Other Outcomes (3)

• Area under the concentration time curve (AUC)

  During Dose Escalation Phase PK blood samples for determination of TAS-119 PK profile will be collected during Cycle 1. In the Expansion Phase, the first 12 patients (DDI Subgroup) will undergo PK sampling in Cycle 1 and Cycle 2 (up to 31 days).

• Maximum Plasma Concentration (Cmax)

  During Dose Escalation Phase PK blood samples for determination of TAS-119 PK profile will be collected during Cycle 1. In the Expansion Phase, the first 12 patients (DDI Subgroup) will undergo PK sampling in Cycle 1 and Cycle 2 (up to 31 days).

• Time of maximum observed serum concentration (Tmax)

  During Dose Escalation Phase PK blood samples for determination of TAS-119 PK profile will be collected during Cycle 1. In the Expansion Phase, the first 12 patients (DDI Subgroup) will undergo PK sampling in Cycle 1 and Cycle 2 (up to 31 days).

Study Arms (1)

TAS-119

EXPERIMENTAL

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

Interventions

TAS-119 DRUG

TAS-119

Paclitaxel DRUG

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

Also known as: Taxol

TAS-119

Eligibility Criteria

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

You may qualify if:

• Is a male or female ≥ 18 years of age, that has provided written informed consent.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (4)

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Washington University School of Medicine Division of Oncology Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Neoplasms; Epilepsy

Interventions

TAS-119; Paclitaxel

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

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

Study Record Dates

• First Submitted: April 28, 2014
• First Posted: May 8, 2014
• Study Start: August 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: September 5, 2024

Record last verified: 2024-08

Locations

US (4)