NCT00422097

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1 cancer

Timeline
Completed

Started Jan 2007

Typical duration for phase_1 cancer

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2007

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

January 12, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 15, 2007

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2009

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed
19 days until next milestone

Results Posted

Study results publicly available

April 20, 2011

Completed
Last Updated

March 10, 2016

Status Verified

February 1, 2016

Enrollment Period

2.6 years

First QC Date

January 12, 2007

Results QC Date

January 27, 2011

Last Update Submit

February 9, 2016

Conditions

Cancer

Outcome Measures

Primary Outcomes (2)

  • Maximum Tolerated Dose (MTD) of Ixabepilone

    MTD is based on Cycle 1 data only and defined as the maximum dose that can be administered to 6 participants with no more than 1 experiencing a dose-limiting toxicity (DLT) (or fewer than one third of participants if more than 6 receive treatment) with at least 2 participants experiencing a DLT at the next higher dose level. DLT=an event, such as neutropenia; thrombocytopenia; Gr 3 or 4 nausea or diarrhea; Gr 3 fatigue or asthenia; transient arthralgia or recalcitrant myalgia; and prolonged recovery from a toxicity, that occurs during the first course of treatment.

    Days 1 through 21 (Cycle 1)

  • Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade

    Adverse events (AEs) graded by CTC version 3. Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=life threatening; Gr 5=Death related to AE. DLT is defined as an event related to ixabepilone that occurs during the first course of treatment. Includes neutropenia; thrombocytopenia; Gr 3 or 4 nausea, vomiting, or diarrhea despite adequate medical intervention and prophylaxis; Gr 3 fatigue or asthenia; transient arthralgia or myalgia unresponsive to medical intervention; any Gr 3 nonhematologic toxicity; and prolonged recovery from a toxicity.

    Days 1 through 21 (Cycle 1), continuously

Secondary Outcomes (14)

  • Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation

    Days 1 through 21 (Cycle 1), continuously

  • Number of Participants With Abnormal Laboratory Values by Worst CTC Grade

    Baseline and Days 1, 8, and 15 of Cycle 1 (21 days)

  • Maximum Plasma Concentration (Cmax) of Ixabepilone

    Days 1 and 5 of Cycle 1

  • Time of Maximum Plasma Concentration (Tmax) of Ixabepilone

    Days 1 and 5 of Cycle 1

  • Area Under the Concentration-time Curve in 1 Dosing Interval (AUC[TAU])of Ixabepilone

    Days 1 and 5 of Cycle 1

  • +9 more secondary outcomes

Study Arms (8)

Ixabepilone, 5 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 5 mg/d

Ixabepilone, 10 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 10 mg/d

Ixabepilone, 15 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 15 mg/d

Ixabepilone, 20 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 20 mg/d

Ixabepilone, 25 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 25 mg/d

Ixabepilone, 30 mg/d

EXPERIMENTAL

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.

Drug: Ixabepilone, 30 mg/d

Ixabepilone, 25 mg, with famotidine

EXPERIMENTAL

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.

Drug: Ixabepilone, 25 mg, with famotidine

Ixabepilone, 25 mg, with food

EXPERIMENTAL

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.

Drug: Ixabepilone, 25 mg, with food

Interventions

Ixabepilone, 5 mg/dDRUG

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, 5 mg/d
Ixabepilone, 10 mg/dDRUG

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, 10 mg/d
Ixabepilone, 15 mg/dDRUG

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, 15 mg/d
Ixabepilone, 20 mg/dDRUG

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, 20 mg/d
Ixabepilone, 25 mg/dDRUG

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, 25 mg/d
Ixabepilone, 30 mg/dDRUG

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, 30 mg/d
Ixabepilone, 25 mg, with famotidineDRUG

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 famotidine
Ixabepilone, 25 mg, with foodDRUG

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.

Ixabepilone, 25 mg, with food

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Wayne State University (Hwcrc)

Detroit, Michigan, 48201, United States

Location

Related Links

MeSH Terms

Conditions

Neoplasms

Interventions

ixabepiloneFamotidineFood

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Results Point of Contact

Title
BMS Study Director
Organization
Bristol-Myers Squibb
Clinical.Trials@bms.com

Study Officials

  • Bristol-Myers Squibb

    Bristol-Myers Squibb

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

January 12, 2007

First Posted

January 15, 2007

Study Start

January 1, 2007

Primary Completion

August 1, 2009

Study Completion

April 1, 2011

Last Updated

March 10, 2016

Results First Posted

April 20, 2011

Record last verified: 2016-02

Locations

US(2)