A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer

R-Pharm

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Drug: Ixabepilone, 25 mg, with food; Drug: Ixabepilone, 5 mg/d; Drug: Ixabepilone, 25 mg, with famotidine; Drug: Ixabepilone, 30 mg/d; Drug: Ixabepilone, 25 mg/d; Drug: Ixabepilone, 15 mg/d; Drug: Ixabepilone, 20 mg/d; Drug: Ixabepilone, 10 mg/d

Study type: Interventional

Funder types: Industry

Identifiers

NCT00422097

CA163-111

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 8 patient groups

Ixabepilone, 5 mg/d

Experimental group

Description:

If none of first 3 participants experiences a dose-limiting toxicity (DLT) during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the maximum tolerated dose (MTD). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 5 mg/d

Ixabepilone, 10 mg/d

Experimental group

Description:

If none of first 3 participants experiences a DLT during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 10 mg/d

Ixabepilone, 15 mg/d

Experimental group

Description:

If none of first 3 participants experiences a DLT during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 15 mg/d

Ixabepilone, 20 mg/d

Experimental group

Description:

If none of first 3 participants experiences a DLT during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 20 mg/d

Ixabepilone, 25 mg/d

Experimental group

Description:

If none of first 3 participants experiences a DLT during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 25 mg/d

Ixabepilone, 30 mg/d

Experimental group

Description:

If none of first 3 participants experiences a DLT during the first 21-day cycle, a new cohort is opened at the next dose level (5-mg increments). If 2 or more of the first 3 participants experience a DLT within the first 21-day course, the dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD.

Treatment:

Drug: Ixabepilone, 30 mg/d

Ixabepilone, 25 mg, with famotidine

Experimental group

Description:

Following identification of MTD, participants who completed Cycle 1 and treated at the ixabepilone MTD (25 mg/d) will crossover to Cycle 2 in which they receive famotidine, 40 mg on Day 1.

Treatment:

Drug: Ixabepilone, 25 mg, with famotidine

Ixabepilone, 25 mg, with food

Experimental group

Description:

Following identification of MTD, participants who completed Cycle 1 and treated at the ixabepilone MTD (25 mg/d) will crossover to Cycle 2 in which they receive a low-fat meal on Day 1.

Treatment:

Drug: Ixabepilone, 25 mg, with food