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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02134067
Recruitment Status : Terminated
First Posted : May 8, 2014
Last Update Posted : February 21, 2020
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Study Description
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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


Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: TAS-119 Drug: Paclitaxel Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Non-Randomized, Dose-Escalating Safety, Tolerability and Pharmacokinetic Study of TAS-119 in Combination With Paclitaxel in Patients With Advanced Solid Tumors
Actual Study Start Date : August 2014
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety
Drug Information available for: Paclitaxel

Arms and Interventions
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Arm Intervention/treatment
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 Name: Taxol


Outcome Measures
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Primary Outcome Measures :
  1. Safety and tolerability of TAS-119 in combination with paclitaxel [ Time Frame: 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). ]

    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.



Secondary Outcome Measures :
  1. Overall response according to RECIST guidelines (version 1.1, 2009) [ Time Frame: 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) ]
    The determination of antitumor efficacy will be based on objective tumor assessments made by the investigator according to RECIST guidelines (version 1.1, 2009).


Other Outcome Measures:
  1. Area under the concentration time curve (AUC) [ Time Frame: 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). ]
    During Dose Escalation Phase PK blood samples will be collected from each arm during Cycle 1 (predose up to 24 hours post-dose). In the Expansion Phase, the first 12 patients (DDI Subgroup) of each arm will undergo PK sampling in Cycle 1 (predose up to 24 hours) and Cycle 2 (predose up to 48 hours post-dose).

  2. Maximum Plasma Concentration (Cmax) [ Time Frame: 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). ]
    During Dose Escalation Phase PK blood samples will be collected from each arm during Cycle 1 (predose up to 24 hours post-dose). In the Expansion Phase, the first 12 patients (DDI Subgroup) of each arm will undergo PK sampling in Cycle 1 (predose up to 24 hours) and Cycle 2 (predose up to 48 hours post-dose).

  3. Time of maximum observed serum concentration (Tmax) [ Time Frame: 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). ]
    During Dose Escalation Phase PK blood samples will be collected from each arm during Cycle 1 (predose up to 24 hours post-dose). In the Expansion Phase, the first 12 patients (DDI Subgroup) of each arm will undergo PK sampling in Cycle 1 (predose up to 24 hours) and Cycle 2 (predose up to 48 hours post-dose).


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02134067


Locations
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United States, Colorado
University of Colorado Hospital Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Missouri
Washington University School of Medicine Division of Oncology Siteman Cancer Center
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Taiho Oncology, Inc.
More Information
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Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02134067    
Other Study ID Numbers: TO-TAS-119-101
First Posted: May 8, 2014    Key Record Dates
Last Update Posted: February 21, 2020
Last Verified: February 2020
Keywords provided by Taiho Oncology, Inc.:
advanced solid tumors
tumor
Dose Escalation
TAS-119
 Taxane
Paclitaxel
Aurora A kinase inhibitor
AurA
Additional relevant MeSH terms:
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Neoplasms
Paclitaxel
TAS-119
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors