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

Sponsor

Odonate Therapeutics, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT04312282

Collaborator

(none)

Enrollment

Locations

Arms

15.3

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: Tesetaxel Drug: Tesetaxel Drug: Itraconazole Drug: Rifampin	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

93 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 6, 2020

Actual Primary Completion Date :

Sep 30, 2020

Actual Study Completion Date :

Jun 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Tesetaxel Tesetaxel orally on Day 1 of a 21-day cycle
Experimental: 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	Drug: Tesetaxel Tesetaxel orally on Day 1 of a 21-day cycle
Experimental: 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	Drug: Tesetaxel Tesetaxel orally on Day 1 of a 21-day cycle Drug: Itraconazole Itraconazole orally once daily from Day -3 to Day 14 of a 21-day cycle
Experimental: 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	Drug: Tesetaxel Tesetaxel orally on Day 1 of a 21-day cycle Drug: Rifampin Rifampin orally once daily from Day -6 to Day 14 of a 21-day cycle

Outcome Measures

Primary Outcome Measures

All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval [Approximately 3 weeks]
Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions [Approximately 6 weeks]
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]
Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole [Approximately 6 weeks]
Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole [Approximately 6 weeks]
Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin [Approximately 6 weeks]
Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin [Approximately 6 weeks]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	START Midwest	Grand Rapids	Michigan	United States	49546
2	Mary Crowley Cancer Research	Dallas	Texas	United States	75320
3	NEXT Oncology	San Antonio	Texas	United States	78229