Clinical trial NCT04312282: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: tesetaxel
itraconazole
rifampin
food effect
QTc interval
food-drug interaction
drug-drug interaction
PK
tesetaxel metabolites
advanced solid tumor
Lead sponsor: Odonate Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-18
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval
timeFrame: Approximately 3 weeks
measure: Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions
timeFrame: Approximately 6 weeks
measure: 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
timeFrame: Approximately 6 weeks
measure: Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole
timeFrame: Approximately 6 weeks
measure: Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole
timeFrame: Approximately 6 weeks
measure: Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin
timeFrame: Approximately 6 weeks
measure: Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin
timeFrame: Approximately 6 weeks
Secondary outcomes:
measure: All Cohorts: Cmax for tesetaxel metabolites
timeFrame: Approximately 6 weeks
measure: All Cohorts: AUC for tesetaxel metabolites
timeFrame: Approximately 6 weeks
measure: All Cohorts: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)
timeFrame: Baseline through 30 days after last administration of Study treatment
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Odonate Therapeutics, Inc.
name: Joseph O'Connell, M.D.
role: STUDY_DIRECTOR
References: