Clinical Study of Ixabepilone Administered as a 24 Hour Infusion in Patients With Solid Malignancies.

Study Overview
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Brief Summary
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The purpose of this study is to determine the dose limiting toxicities, minimum tolerated dose and recommended dose for Phase II studies.

Official Title
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Phase I Study of Ixabepilone Administered as a 24-Hour Infusion in Patients With Advanced Solid Malignancies

Conditions
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Solid Malignancies

Intervention / Treatment
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* Drug: Ixabepilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis of a primary solid tumor measurable or non-measurable disease progressive disease men and women greater or equal to 18 years of age. Exclusion Criteria: women of child bearing potential who are not using birth control women who are pregnant or breast feeding women with a positive pregnancy test on enrollment patients with brain metastasis prior treatment with Ixabepilone known history of human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br> | Drug: Ixabepilone<br>* Intravenous (IV) Infusion; 10, 20, 30, 35, 40 & 45 mg/m2, once every 21 days (1 cycle), up to 9 cycles<br>* Other names: IXEMPRA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities at Dose Level | Dose limiting toxicities=any of the following events attributed to Ixabepilone occuring during the first cycle: grade 3/4 nausea, vomiting, or diarrhea despite medical intervention and/or prophylaxis; other Grade ≥3 nonhematological toxicity; any toxicity requiring study therapy discontinuation; delayed recovery from study therapy-related toxicity which delays scheduled re-treatment for >14 days; Grade 4 neutropenia for ≥5 consecutive days; grade 3/4 neutropenia with sepsis or a fever ≥38.5 C; thrombocytopenia <25,000 cells/mm3 or bleeding requiring a platelet transfusion. | Measures taken at Cycle 01 (21-day cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Related Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Adverse events (AEs) and Serious AEs (SAEs) considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). | From time of screening through post study follow-up at a maximum of 21 9-day cycles. Toxicity assessments occured at least every 4 weeks until all study drug related toxicities. | 
| Hematology Results - Worst On-Study Grade | Worst on-study grade based on laboratory values graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). | Baseline (within 2 weeks of dosing), weekly, and within 72 hours prior to each subsequent 21-day cycle. If CTC Grade 4 hematologic toxicity is observed, complete blood count plus differential and platelets repeated every 3 days until resolution. | 
| Mean Plasma Concentration of Ixabepilone at 40 mg/m2 Dose Level | Mean concentrations over full time period for the 40 mg/mg2 dose level, established as the Maximum Tolerated Dose. (The Maximum Tolerated Dose was established as 40 mg/m2, based on an investiagtion of Dose Limiting Toxicities, which consisted of Febrile Neutropenia (at 40 mg/m2) in 1 participant and Grade 4 neutropenia lasting ≥5 days (at 45 mg/m2)in 2 participants.) | through 72 hours after start of infusion | 
| Best Tumor Response, According to Response Evaluation Criteria in Solid Tumors (RECIST) | RECIST criteria, wherein complete response = disappearance of all target lesions; partial response = 30% decrease in the sum of the longest diameter of target lesions; progressive disease = 20% increase in the sum of the longest diameter of target lesions, and stable disease = small changes that do not meet above criteria. | At Baseline (up to 2 weeks prior to starting therapy), after every 2nd cycle, and at post study follow-upn after a maximum of 9 cycles. |