Phase 1 Trial of Oral Ixabepilone
This study has been terminated.
(Business Objectives Changed)
Sponsor:
Bristol-Myers Squibb
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00632424
First received: March 3, 2008
Last updated: November 4, 2010
Last verified: November 2010
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
This Phase 1 study of oral ixabepilone given every 6 hours for 3 doses on Day 1, every 21 days, was a dose-finding study designed to determine the maximum tolerated dose (MTD) and safety of this dosing schedule in participants with advanced cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Solid Tumors |
Drug: Ixabepilone (oral formulation) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1 Study of Ixabepilone Administered as 3 Oral Doses Each Separated by 6 Hours Every 21 Days in Subjects With Advanced Cancer |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Number of Participants With a Dose-Limiting Toxicity (DLT) [ Time Frame: During Cycle 1 (Day 0 through Day 21) ] [ Designated as safety issue: Yes ]DLT: any of the following, considered related to ixabepilone, occurring in Cycle 1: Absolute neutrophil count (ANC) <500 cells/mm^3 for ≥5 consecutive days or febrile neutropenia of any duration; Grade(Gr)4 thrombocytopenia <25,000 cells/mm^3 or Gr3 with bleeding requiring platelet transfusion; Gr3/4 nausea, vomiting, or diarrhea despite use of adequate intervention, fatigue, any other clinically significant drug-related ≥Gr 3 non-hematologic toxicity, delayed recovery (to Gr ≤1 or baseline, except alopecia) from toxicity which delays initiation of Cycle 2 by ≥3 weeks.
- Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD) [ Time Frame: At the end of Cycle 1 (21 days). ] [ Designated as safety issue: Yes ]The MTD was defined as the maximum dose which could be given to 6 participants such that not more than 1 participant experienced a DLT (or fewer than one-third if there were more than 6 treated participants) with at least 2 participants experiencing a DLT at the next higher dose level. The R2PD was to be based on the MTD and the assessment of any relevant chronic toxicities.
Secondary Outcome Measures:
- Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE [ Time Frame: From first study drug administration through 30 days post dose ] [ Designated as safety issue: Yes ]AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.
- Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%) [ Time Frame: From first study drug administration through 30 days post dose ] [ Designated as safety issue: Yes ]AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.
- Number of Participants With Hematology Laboratory Abnormalities [ Time Frame: From first study drug administration through 30 days post dose ] [ Designated as safety issue: Yes ]Laboratory results were graded according to CTC v 3.0. Hematology laboratory evaluations included absolute neutrophil count (ANC), white blood cell count (WBC), platelets (PLT), and hemoglobin (HGB).
- Number Of Participants With Liver Function and Renal Laboratory Abnormalities [ Time Frame: From first study drug administration through 30 days post dose ] [ Designated as safety issue: Yes ]Laboratory results were graded according to CTC v 3.0. Clinical laboratory evaluations included liver function (alanine aminotransferase [ALT], Aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin), and renal function (creatinine).
- Maximum QTc Interval on Day 1 and Maximum Change From Baseline for QTc Interval [ Time Frame: Baseline (Day -1) and Day 1 ] [ Designated as safety issue: Yes ]QTc interval was defined as the measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, corrected for heart rate
- PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time [ Time Frame: Time 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 12.5, 13, 14, 15, 16, 17, 18, 20, 48, 72, and 168 hours post dose ] [ Designated as safety issue: No ]Pharmacokinetics (PK) of ixabepilone were derived from plasma concentration versus time data. Individual patient PK parameter values were derived by standard non-compartmental methods by a validated pharmacokinetic analysis program. PK parameters include Cmax (maximum plasma concentration), Cmin (minimum plasma concentration), Tmax (time of maximum plasma concentration), AUC (0-TAU) (area under the curve in one dosing interval), T-half (plasma half-life).
- Best Overall Response [ Time Frame: Tumor assessments performed on Day 1 of every other cycle of therapy, until disease progression or toxicity ] [ Designated as safety issue: No ]Tumor assessment was performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all clinical and radiological evidence of target lesions; Partial Response (PR) = at least 30% reduction in the sum of the longest diameter of all target lesions; Progressive disease (PD) = at least 20% increase in the sum of the longest diameter of all target lesions; Stable Disease (SD) = neither PR nor PD criteria were met.
| Enrollment: | 23 |
| Study Start Date: | May 2008 |
| Study Completion Date: | June 2009 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: Ixabepilone (oral formulation)
Capsules, Oral, Dose escalating (Phase 1), 3 doses on 1 day every 3 weeks, until disease progression or unacceptable toxicity
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Males and females, 18 or older
- Histologically or cytologically confirmed diagnosis of solid tumor malignancy
- Measurable or non-measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- Karnofsky Performance Status (KPS) of 70-100
- Recovered from toxicities resulting from previous therapies
Exclusion Criteria:
- More than 3 prior cytotoxic regimens in the metastatic setting
- Current or recent gastrointestinal (GI) disease that would impact the absorption of study drug
- Inability to swallow whole capsules
- Inadequate hepatic and renal function
- Function exposure to any epothilone
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00632424
Locations
| United States, California | |
| Stanford University | |
| Stanford, California, United States, 94305 | |
| United States, District of Columbia | |
| Georgetown University Medical Center | |
| Washington, District of Columbia, United States, 20007 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Study Director, Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00632424 History of Changes |
| Other Study ID Numbers: | CA163-149 |
| Study First Received: | March 3, 2008 |
| Results First Received: | September 15, 2010 |
| Last Updated: | November 4, 2010 |
| Health Authority: | United States: Food and Drug Administration |
ClinicalTrials.gov processed this record on May 23, 2013