Phase 1 Trial of Oral Ixabepilone

This study has been terminated.
(Business Objectives Changed)
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00632424
First received: March 3, 2008
Last updated: November 4, 2010
Last verified: November 2010
  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:
  • IXEMPRA
  • BMS-247550

  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 April 17, 2014