Phase 1 Trial of Oral Ixabepilone
- Registration Number
- NCT00632424
- Lead Sponsor
- R-Pharm
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 23
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Ixabepilone (oral formulation) -
- Primary Outcome Measures
Name Time Method Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 (Day 0 through Day 21) 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) At the end of Cycle 1 (21 days). 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
Name Time Method 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 From first study drug administration through 30 days post dose 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%) From first study drug administration through 30 days post dose 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 Liver Function and Renal Laboratory Abnormalities From first study drug administration through 30 days post dose 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 Baseline (Day -1) and Day 1 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 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 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 Tumor assessments performed on Day 1 of every other cycle of therapy, until disease progression or toxicity 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.
Number of Participants With Hematology Laboratory Abnormalities From first study drug administration through 30 days post dose 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).
Trial Locations
- Locations (2)
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Stanford University
🇺🇸Stanford, California, United States