Clinical Trials /

The Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors

NCT04312282

Description:

This is a 3-cohort, multicenter, Phase 1 study of the effect of tesetaxel, an investigational, orally administered taxane, on the corrected QT (QTc) interval and the potential effect of food, a cytochrome P450 (CYP) 3A inhibitor (itraconazole), and a CYP3A inducer (rifampin) on tesetaxel pharmacokinetics (PK) in adult patients with advanced solid tumors.

Related Conditions:
  • Solid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: The Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors
  • Official Title: An Open-Label Study of the Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ODO-TE-S101
  • NCT ID: NCT04312282

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
TesetaxelCohort 1, Sequence 1A: Fed then fasted
TesetaxelCohort 1, Sequence 1B: Fasted then fed
ItraconazoleCohort 2: Tesetaxel plus itraconazole
RifampinCohort 3: Tesetaxel plus rifampin

Purpose

This is a 3-cohort, multicenter, Phase 1 study of the effect of tesetaxel, an investigational, orally administered taxane, on the corrected QT (QTc) interval and the potential effect of food, a cytochrome P450 (CYP) 3A inhibitor (itraconazole), and a CYP3A inducer (rifampin) on tesetaxel pharmacokinetics (PK) in adult patients with advanced solid tumors.

Detailed Description

      Cohort 1:

      Cohort 1 is a 2-period, 2-sequence, crossover study designed to assess the effect of food on
      the PK of tesetaxel and tesetaxel metabolites. Patients will be randomized in a 1:2 ratio to
      receive tesetaxel on Day 1 of two 21-day cycles under fed and fasting conditions in one of
      two opposing sequences (Sequence 1A and Sequence 1B).

      Cohort 2:

      Cohort 2 is a 2-period, single-sequence, crossover study designed to assess the potential PK
      drug-drug interaction (DDI) of a strong CYP3A inhibitor (itraconazole) on tesetaxel and
      tesetaxel metabolites. Patients will receive tesetaxel during Cycle 1 followed by a reduced
      dose of tesetaxel plus itraconazole during Cycle 2.

      Cohort 3:

      Cohort 3 is a 2-period, single-sequence, crossover study designed to assess the potential PK
      DDI of a strong CYP3A inducer (rifampin) on tesetaxel and tesetaxel metabolites. Patients
      will receive tesetaxel during Cycle 1 followed by tesetaxel plus rifampin during Cycle 2.

      Patients in all cohorts will also participate in a study designed to assess the effect of
      tesetaxel and tesetaxel metabolites on cardiac repolarization as measured by the change from
      baseline in the QTc interval over the first cycle of treatment. Patients who are tolerating
      and benefitting from treatment with tesetaxel will have the opportunity to continue onto an
      optional treatment extension.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1, Sequence 1A: Fed then fastedExperimentalCycle 1: Tesetaxel on Day 1 of a 21-day cycle under fed conditions Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions
  • Tesetaxel
Cohort 1, Sequence 1B: Fasted then fedExperimentalCycle 1: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fed conditions
  • Tesetaxel
Cohort 2: Tesetaxel plus itraconazoleExperimentalCycle 1: Tesetaxel on Day 1 of a 21-day cycle Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and itraconazole on Day -3 through Day 14 of a 21-day cycle
  • Tesetaxel
  • Itraconazole
Cohort 3: Tesetaxel plus rifampinExperimentalCycle 1: Tesetaxel on Day 1 of a 21-day cycle Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and rifampin on Day -6 through Day 14 of a 21-day cycle
  • Tesetaxel
  • Rifampin

Eligibility Criteria

        Inclusion Criteria:

          -  Female or male patients at least 18 years of age

          -  Histologically or cytologically confirmed solid tumor

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  Adequate cardiac conduction by ECG

          -  Adequate bone marrow, hepatic, and renal function

        Exclusion Criteria:

          -  Presence of risk factors for QTc prolongation

          -  Presence of neuropathy Grade > 1

          -  Anticancer treatment ≤ 14 days prior to randomization

          -  Major surgery ≤ 28 days prior to randomization

          -  Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of:

               -  A moderate or strong inhibitor or inducer of CYP3A

               -  A CYP3A substrate with a narrow therapeutic range or that is contraindicated with
                  either itraconazole or rifampin
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval
Time Frame:Approximately 3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:All Cohorts: Cmax for tesetaxel metabolites
Time Frame:Approximately 6 weeks
Safety Issue:
Description:
Measure:All Cohorts: AUC for tesetaxel metabolites
Time Frame:Approximately 6 weeks
Safety Issue:
Description:
Measure:All Cohorts: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)
Time Frame:Baseline through 30 days after last administration of Study treatment
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Odonate Therapeutics, Inc.

Trial Keywords

  • tesetaxel
  • itraconazole
  • rifampin
  • food effect
  • QTc interval
  • food-drug interaction
  • drug-drug interaction
  • PK
  • tesetaxel metabolites
  • advanced solid tumor

Last Updated

March 16, 2020