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

NCT ID: NCT00422097

Last Updated: 2016-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2011-04-30

Brief 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.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ixabepilone, 5 mg/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 5 mg/d

Intervention Type: DRUG

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/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 10 mg/d

Intervention Type: DRUG

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/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 15 mg/d

Intervention Type: DRUG

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/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 20 mg/d

Intervention Type: DRUG

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/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 25 mg/d

Intervention Type: DRUG

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/d

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.

Group Type: EXPERIMENTAL

Ixabepilone, 30 mg/d

Intervention Type: DRUG

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.

Ixabepilone, 25 mg, with famotidine

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.

Group Type: EXPERIMENTAL

Ixabepilone, 25 mg, with famotidine

Intervention Type: DRUG

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.

Ixabepilone, 25 mg, with food

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.

Group Type: EXPERIMENTAL

Ixabepilone, 25 mg, with food

Intervention Type: DRUG

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.

Interventions

Ixabepilone, 5 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 10 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 15 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 20 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 25 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 30 mg/d

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.

Intervention Type: DRUG

Ixabepilone, 25 mg, with famotidine

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.

Intervention Type: DRUG

Ixabepilone, 25 mg, with food

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 Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

R-Pharm

INDUSTRY

Sponsor Role: lead

Responsible Party

Bristol-Myers Squibb

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Wayne State University (Hwcrc)

Detroit, Michigan, United States

Countries

United States

Related Links

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

CA163-111

Identifier Type: -

Identifier Source: org_study_id