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

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

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.

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.

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