MC# 20-02 - 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 Solid Tumors

  • Agent(s): Tesetaxel
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Cytotoxic Therapy
  • Molecular Target(s): n/a

Mechanism of Action

Tesetaxel is a semi-synthetic bioavailable taxane derivative that binds to and stabilizes tubulin, promoting microtubule assembly and thereby preventing microtubule depolymerization.  This may lead to cell cycle arrest and an inhibition of cell proliferation.

Purpose

In this study, the sponsor and investigators want to learn:

  • The safety and tolerability tesetaxel 
  • How much of tesetaxel is absorbed into the blood and how fast it is removed when given with rifampin and itraconazole and with or without food
  • The effects of tesetaxel on the electrical activity of the heart
Inclusion Criteria
  • Female or male patients at least 18 years of age
  • Any histologically or cytologically confirmed solid tumor for which no standard therapy exists (including surgery or radiotherapy)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Patients must have expected time on Study of at least 12 weeks
  • Adequate cardiac conduction by ECG without evidence of second- or third-degree atrioventricular block and meeting all of the following ECG criteria:​​​​​​
    • Heart rate 45-100 beats per minute
    • QRS interval ≤110 milliseconds (msec)
    • QT interval corrected for heart rate by Fridericia’s formula (QTcF) ≤450 msec for men and ≤480 msec for women
    • PR interval ≤200 msec
    • No arrhythmia as interpreted by the Investigator or site cardiologist
  • Known metastases to the CNS are permitted.  The following criteria apply:
    • Patients must be neurologically stable and off corticosteroids for at least 7 days prior to Randomization
    • Any radiographically evident CNS cancer must not be progressing radiographically on the most recent scan
    • Patients with a history of CNS metastases but with no current evidence of CNS lesions following local therapy are eligible
    • Patients with current evidence of leptomeningeal disease are not eligible
    • Any prior whole brain radiation therapy must have been completed >14 days prior to the date of Randomization
    • Prior stereotactic brain radiosurgery is permitted
    • CNS surgical resection must have been completed >28 days prior to the date of Randomization; patient must have complete recovery from surgery
  • Adequate hematologic, hepatic, and renal function, as evidenced by:
    • Absolute neutrophil count (ANC) ≥1,500/μL without colony-stimulating factor support
    • Platelet count ≥100,000/μL
    • Hemoglobin ≥9.0 g/dL without transfusion support at frequency of more than 2 units of packed red blood cells (PRBCs) every 6 weeks
    • Total bilirubin <1.5 × upper limit of normal (ULN); does not apply to patients with Gilbert’s syndrome
    • Alanine aminotransferase (ALT) <3 × ULN unless hepatic metastases are present, then <5 × ULN
    • Aspartate aminotransferase (AST) <3 × ULN unless hepatic metastases are present, then <5 × ULN
    • Alkaline phosphatase <2.5 × ULN unless: (1) hepatic metastases are present, then <5 × ULN; or (2) bone metastases are present and total bilirubin, ALT and AST ≤ULN
    • Calculated creatinine clearance ≥50 mL/min (by Cockcroft-Gault formula or local standard)
    • Serum albumin ≥2.5 g/dL
    • Prothrombin time (PT) ≤1.5 × ULN or international normalized ratio (INR) ≤1.3, and partial thromboplastin time (PTT) ≤1.5 × ULN, unless the patient is on a therapeutic anticoagulant 
  • Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 from adverse effects of prior surgery, radiotherapy, hormonal therapy, and other therapy, as applicable, with the exception of: (1) Grade 2 alopecia from prior chemotherapy or radiotherapy; (2) Grade 2 lymphopenia; or (3) well-controlled Grade 2 endocrine toxicity from prior treatment with immune checkpoint inhibitors
  • Ability to swallow an oral solid-dosage form of medication
  • A negative serum pregnancy test within 3 days prior to the first dose of Study treatment in women of childbearing potential (ie, all women except those who are postmenopausal for ≥1 year or who have a history of hysterectomy or surgical sterilization)
  • Women of childbearing potential must use an effective form of contraception from Screening throughout the Treatment Phase and until 70 days after the last dose of Study treatment
    • Acceptable methods include: intrauterine device (must be non-hormonal intrauterine device for patients who have HR positive MBC) or double barrier methods, including male/female condoms with spermicide and use of contraceptive sponge, cervical cap, diaphragm, abstinence, tubal ligation or occlusion, or intercourse with a male partner who has had a vasectomy with medical confirmation of surgical success
    • In regions which mandate the use of a highly effective methods of contraception the following are options: copper intrauterine device, tubal ligation or occlusion, intercourse with a partner who has undergone vasectomy (with confirmation of surgical success), or abstinence
  • Men must use an effective form of contraception from Screening throughout the Treatment Phase and until 130 days after the last dose of Study treatment
    • Acceptable methods include: male/female condoms with spermicide, abstinence, vasectomy with medical confirmation of surgical success, or intercourse with a female partner who is taking an oral hormone contraceptive, has an implanted hormone contraceptive, or has undergone placement of an intrauterine device or tubal ligation or occlusion
    • In regions which mandate the use of a highly effective methods of contraception the following are options: intercourse with a female partner who has undergone placement of an intrauterine device or bilateral tubal ligation or occlusion, sexual abstinence, or vasectomy with medical confirmation of surgical success
  • Written informed consent and authorization to use and disclose health information
  • Ability to comprehend and comply with the requirements of the Study
Exclusion Criteria
  • Any of the following risk factors for QTc prolongation:
    • Marked prolongation of QTcF interval (QTcF interval >450 msec for men and >480 msec for women) during Screening
    • History of risk factors for torsades de pointes (TdP), such as history of ventricular dysfunction or congestive heart failure, cardiac ischemia, recent (within prior 6 months) myocardial infarction (MI), or family history of Long QT Syndrome
    • Uncontrolled electrolyte disorders, which, in the Investigator’s opinion, might lead to alteration in the QT interval
    • Concurrent therapy with antiarrhythmic drugs or other medications that prolong the QT interval unless ECG meets inclusion criteria on a stable dose of the drug and the site has obtained agreement from the Sponsor medical team
    • Implantable pacemaker or automatic implantable cardioverter defibrillator (AICD), bradycardia (defined as <45 beats per minute), personal history of unexplained syncope within the last year prior to the first dose of Study treatment, and patients with other significant cardiac disease or disorders that, in the Investigator’s opinion, should exclude the patient from the Study
  • Patients with a severe acute or chronic medical condition (including gastric resection) or psychiatric condition or laboratory abnormality that may increase the risk associated with Study participation or investigational product administration or may interfere with the interpretation of Study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this Study
  • Presence of neuropathy >Grade 1 per NCI CTCAE version 5.0
  • Anticancer treatment, including hormonal therapy, radiotherapy, chemotherapy, biologic therapy, or therapy in an investigational clinical study, ≤14 days prior to Randomization
  • Major surgery ≤28 days prior to Randomization; patient must have complete recovery from surgery
  • History of hypersensitivity to taxanes; hypersensitivity to the solvent does not preclude patient participation in this Study
  • History of hypersensitivity to itraconazole, any of its excipients, or any other azole antifungals, or any contraindication to itraconazole administration according to the current package insert (or regulatory equivalent) for itraconazole
  • History of hypersensitivity to rifampin, any of its excipients, or any other rifamycins, or any contraindication to rifampin administration according to the current package insert (or regulatory equivalent) for rifampin
  • Pregnant or breastfeeding
  • If, in the opinion of the Investigator, the patient is deemed unwilling or unable to comply with the requirements of the Study
  • Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of:
    • A medication, beverage, or food that is a moderate or strong inhibitor or inducer of CYP3A (patients should discontinue taking any regularly-taken medication that is a moderate or strong inhibitor or inducer of the CYP3A);
    • A medication that is a CYP3A substrate with a narrow therapeutic range or is contraindicated with either itraconazole or rifampin, including, but not limited to, ergot alkaloids, nevirapine, antiretrovirals, histamine H2 antagonists, and proton-pump inhibitors; or
    • Other concomitant medications not approved by the Sponsor

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City

Contact Us About This Trial

Reach out to us by sharing your info in the form below or give us a call at 972-566-3000.

Re: MC# 20-02