A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer
Condition: Cancer
Intervention: Ixabepilone, 5 mg/d; Ixabepilone, 10 mg/d; Ixabepilone, 15 mg/d; Ixabepilone, 20 mg/d; Ixabepilone, 25 mg/d; Ixabepilone, 30 mg/d; Ixabepilone, 25 mg, with famotidine; Ixabepilone, 25 mg, with food
Intervention description: Ixabepilone, 5 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Ixabepilone, 10 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Ixabepilone, 15 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Ixabepilone, 20 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Ixabepilone, 25 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Ixabepilone, 30 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.; Participants crossed over from Cycle 1 to receive famotidine, 40 mg, in an oral dose given 2 hours before ixabepilone, 25 mg, on Day 1 of Cycle 2 only.; Participants consume a low-fat meal starting 30 minutes before dose administration on Day 1 of Cycle 2. Food consumed within 30 minutes. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.
Intervention MeSH terms: Epothilones; Famotidine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will determine the maximum tolerated dose of oral ixabepilone administered for 5
      successive days every 21 days in participants with advanced cancer. The safety, tolerability,
      and pharmacokinetics of ixabepilone in the body will be studied. In addition, this study will
      assess preliminary evidence of the effect of food and famotidine on the pharmacokinetics of
      oral ixabepilone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of solid tumor malignancy unresponsive to current treatment
             options

          -  Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in
             Solid Tumors

          -  Lapse of at least 1 week since minor surgery and of at least 3 weeks since major
             surgery and radiation therapy

          -  Eastern Cooperative Oncology Group performance status of 0-1

          -  Lapse of at least 4 weeks since immunotherapy or chemotherapy

          -  Negative pregnancy test result within 72 hours of study drug administration for any
             woman of childbearing potential (WOCBP)

        Exclusion Criteria:

          -  WOCBP unable or unwilling to use birth control during study and for up to 4 weeks
             after study completion

          -  Women who are pregnant or breastfeeding

          -  Fertile men not using effective birth control with partners who are WOCBP

          -  Gastrointestinal(GI) disease or GI tract surgery that could impact drug absorption

          -  Inability to swallow capsules

          -  Inability to be venipunctured or to tolerate venous access

          -  Known symptomatic brain metastases

          -  Common Terminology Criteria for Adverse Events Grade 2 or greater neuropathy or
             history of Grade 3 or greater neuropathy

          -  Psychiatric conditions inhibiting compliance with protocol requirements

          -  Uncontrolled medical disorder or active infection that would impair participant's
             ability to receive protocol therapy or whose control may be jeopardized by the study
             treatment protocol

          -  Inadequate hematologic, hepatic, or renal function

          -  History of significant drug allergy

          -  Previous exposure to ixabepilone

          -  Exposure to any investigational drug or placebo within 4 weeks of enrollment

          -  Concurrent chemotherapy regimen

          -  Use of cytochrome P4503A4 inhibitors or inducers within 2 weeks of treatment
             initiation (unless approved by medical monitor)

          -  Use of steroids (except as antiemetic)

          -  Prisoners or subjects involuntarily detained for treatment