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

• ClinicalTrials.gov Identifier: NCT02134067
• Recruitment Status: Terminated
• First Posted: May 8, 2014
• Last Update Posted: February 21, 2020
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Tracking Information

• First Submitted Date: April 28, 2014
• First Posted Date: May 8, 2014
• Last Update Posted Date: February 21, 2020
• Actual Study Start Date: August 2014
• Actual Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2014)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 6, 2014)

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).

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 6, 2014)

• 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).
• 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).
• 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).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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

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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors

Intervention

• Drug: TAS-119
• Drug: Paclitaxel
  A dose of 90 mg/m2 is used in combination with various doses of TAS-119.
  Other Name: Taxol

Study Arms

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.

Interventions:

• Drug: TAS-119
• Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 19, 2020): 30
• Original Estimated Enrollment (submitted: May 6, 2014): 74
• Actual Study Completion Date: July 2018
• Actual Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02134067
• Other Study ID Numbers: TO-TAS-119-101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Taiho Oncology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Taiho Oncology, Inc.
• Verification Date: February 2020