Clinical trial NCT00422097: A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer
Official title: A Phase I Study of Ixabepilone Administered as a Daily Oral Dose on 5 Successive Days Every 21 Days in Subjects With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
First posted: 2007-01-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Ixabepilone
timeFrame: Days 1 through 21 (Cycle 1)
measure: Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
timeFrame: Days 1 through 21 (Cycle 1), continuously
Secondary outcomes:
measure: Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
timeFrame: Days 1 through 21 (Cycle 1), continuously
measure: Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
timeFrame: Baseline and Days 1, 8, and 15 of Cycle 1 (21 days)
measure: Maximum Plasma Concentration (Cmax) of Ixabepilone
timeFrame: Days 1 and 5 of Cycle 1
measure: Time of Maximum Plasma Concentration (Tmax) of Ixabepilone
timeFrame: Days 1 and 5 of Cycle 1
measure: Area Under the Concentration-time Curve in 1 Dosing Interval (AUC[TAU])of Ixabepilone
timeFrame: Days 1 and 5 of Cycle 1
measure: Plasma Half-life (T-Half) of Ixabepilone
timeFrame: Day 5 of Cycle 1
measure: Maximum Plasma Concentration (Cmax) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Time of Maximum Plasma Concentration (Tmax)of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Maximum Plasma Concentration (Cmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Time of Maximum Plasma Concentration (Tmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
timeFrame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)
measure: Number of Participants With Significant Findings on Physical Examination or Electrocardiogram (ECG)
timeFrame: At screening and predose Day 1, Cycle 1 (21 days)
measure: Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
timeFrame: At screening and predose Day 1, Cycle 1 (21 days)
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Detroit
country: United States
facility: Wayne State University (Hwcrc)
state: Michigan
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: