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

Advanced Solid Tumors Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04312282
• Other study ID #: ODO-TE-S101
• Status: Terminated
• Phase: Phase 1
• Start date: March 6, 2020
• Est. completion date: June 15, 2021

Study information

• Verified date: July 2021
• Source: Odonate Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 93
• Est. completion date: June 15, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Tesetaxel
Tesetaxel orally on Day 1 of a 21-day cycle
• Tesetaxel
Tesetaxel orally on Day 1 of a 21-day cycle
• Itraconazole
Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle
• Rifampin
Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Odonate Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cohorts: The change from baseline in Fridericia's corrected QT (?QTcF) interval		Approximately 3 weeks
Primary	Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions		Approximately 6 weeks
Primary	Cohort 1, Sequences 1A and 1B: Area under the plasma concentration-time curve from 0 to the last measurable plasma concentration (AUC0-t) for tesetaxel under fed and fasted conditions		Approximately 6 weeks
Primary	Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole		Approximately 6 weeks
Primary	Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole		Approximately 6 weeks
Primary	Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin		Approximately 6 weeks
Primary	Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin		Approximately 6 weeks
Secondary	All Cohorts: Cmax for tesetaxel metabolites		Approximately 6 weeks
Secondary	All Cohorts: AUC for tesetaxel metabolites		Approximately 6 weeks
Secondary	All Cohorts: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)		Baseline through 30 days after last administration of Study treatment