Clinical Trial: NCT04312282 - My Cancer Genome

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:

Terminated

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04312282

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

Drug	Synonyms	Arms
Tesetaxel		Cohort 1, Sequence 1A: Fed then fasted
Tesetaxel		Cohort 1, Sequence 1B: Fasted then fed
Itraconazole		Cohort 2: Tesetaxel plus itraconazole
Rifampin		Cohort 3: Tesetaxel plus rifampin

Purpose

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 were 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 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
      receive tesetaxel during Cycle 1 followed by tesetaxel plus rifampin during Cycle 2.

      Patients in all cohorts 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 have the opportunity to continue onto an
      optional treatment extension.

Trial Arms

Name	Type	Description	Interventions
Cohort 1, Sequence 1A: Fed then fasted	Experimental	Cycle 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 fed	Experimental	Cycle 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 itraconazole	Experimental	Cycle 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 rifampin	Experimental	Cycle 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:	Terminated
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

July 28, 2021

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