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

NCT ID: NCT04312282

Last Updated: 2021-07-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

93 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-06

Study Completion Date

2021-06-15

Brief Summary

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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

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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.

Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1, Sequence 1A: Fed then fasted

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

Group Type EXPERIMENTAL

Tesetaxel

Intervention Type DRUG

Tesetaxel orally on Day 1 of a 21-day cycle

Cohort 1, Sequence 1B: Fasted then fed

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

Group Type EXPERIMENTAL

Tesetaxel

Intervention Type DRUG

Tesetaxel orally on Day 1 of a 21-day cycle

Cohort 2: Tesetaxel plus itraconazole

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

Group Type EXPERIMENTAL

Tesetaxel

Intervention Type DRUG

Tesetaxel orally on Day 1 of a 21-day cycle

Itraconazole

Intervention Type DRUG

Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle

Cohort 3: Tesetaxel plus rifampin

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

Group Type EXPERIMENTAL

Tesetaxel

Intervention Type DRUG

Tesetaxel orally on Day 1 of a 21-day cycle

Rifampin

Intervention Type DRUG

Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

Interventions

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Tesetaxel

Tesetaxel orally on Day 1 of a 21-day cycle

Intervention Type DRUG

Tesetaxel

Tesetaxel orally on Day 1 of a 21-day cycle

Intervention Type DRUG

Itraconazole

Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle

Intervention Type DRUG

Rifampin

Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Odonate Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joseph O'Connell, M.D.

Role: STUDY_DIRECTOR

Odonate Therapeutics, Inc.

Locations

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START Midwest

Grand Rapids, Michigan, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

NEXT Oncology

San Antonio, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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ODO-TE-S101

Identifier Type: -

Identifier Source: org_study_id

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