Phase 2
Completed N=313
Study to Assess Effectiveness of Giving Combination of Standard Chemotherapy Drugs Versus Combination of Standard Chemotherapy and New Drug Ixabepilone When Given Before Surgical Removal of Early Stage Breast Cancer
Source: ClinicalTrials.gov NCT00455533 ↗Enrolled (actual)
313
Serious AEs
9.7%
Results posted
Apr 2011
Primary outcomePrimary: Percentage of Participants Achieving Pathologic Complete Response (pCR) — 24.3; 25.2 Percentage of Participants — p=0.8921
Summary
The study will evaluate the effectiveness of ixabepilone when given after doxorubicin plus cyclophosphamide (AC) compared to standard treatment of paclitaxel given after doxorubicin plus cyclophosphamide in patients with early stage breast cancer. In addition the study will verify predefined biomarkers as well as discover new biomarkers that could identify patients who are more likely to respond to ixabepilone than standard paclitaxel based therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Pathologic Complete Response (pCR) |
24.3; 25.2 | 0.8921 |
| PRIMARY Percentage of Participants Achieving Pathologic Complete Response (pCR) in Biomarker-Defined Populations |
35.9; 36.1; 17.4; 22.4; 34.9; 35.7 | — |
| PRIMARY Percentage of Participants Achieving Pathologic Complete Response (pCR) in 20- and 26-Gene Model Subgroups |
— | — |
| SECONDARY Percentage of Participants Achieving Clinical Objective Response |
81.1; 77.6 | — |
| SECONDARY Percentage of Participants Requiring Breast Conservation Surgery |
41.9; 32.7 | — |
| SECONDARY Percentage of Participants Achieving Combined pCR and Minimal Residual Cancer Burden (RCB) 1 |
30.4; 33.3 | 0.6186 |
| SECONDARY Randomized Participants With Non-missing pCR & Biomarker Expression (GENE [Probe Set]), to Explore Whether Gene Expression Patterns for GTSE1, Isoforms of β-tubulin, Kallikreins 5, 6, 10 Are Differentially Predictive of pCR |
245; 245; 245; 245; 245; 245 | 0.4115 |
| SECONDARY Randomized Participants With Non-missing pCR & Biomarker Expression (GENE [Probe Set]) to Explore Whether Gene Expression Patterns for GTSE1, Isoforms of β-tubulin, Kallikreins 5, 6, 10 Are Differentially Predictive of pCR/RCB1 |
245; 245; 245; 245; 245; 245 | 0.5604 |
| SECONDARY Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-Specified Thresholds |
0.143; 0.288; 0.323; 0.259; 0.228; 0.284 | — |
| SECONDARY Percentage of Participants With pCR/RCB1 and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds |
0.224; 0.339; 0.371; 0.362; 0.304; 0.363 | — |
| SECONDARY Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds, Estrogen-Receptor (ER) Negative Participants |
0.192; 0.483; 0.447; 0.341; 0.327; 0.417 | — |
| SECONDARY Prevalence of Biomarker Based on Optimal Threshold (Biomarker Positive Participants) |
0.394; 0.299; 0.392; 0.514; 0.486 | — |
| SECONDARY Overall Safety Summary: Deaths, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Drug-Related AEs, and Most Common Treatment-Related Non-Hematologic Adverse Events (TNAEs) Occuring in >=10% of Participants |
0; 2; 0; 0; 2; 0 | — |
| SECONDARY Severity of Any Drug-Related AEs and Gastrointestinal AEs by System Organ Class |
5; 8; 56; 69; 55; 32 | — |
| SECONDARY On-Study Hematology: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase |
32; 32; 27; 63; 32; 41 | — |
| SECONDARY On-Study Liver Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase |
72; 52; 54; 59; 13; 22 | — |
| SECONDARY On-Study Renal Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase |
136; 135; 6; 3; 0; 1 | — |
| SECONDARY Number of Participants by Dose for AC |
145; 144; 145; 144; 145; 142 | — |
| SECONDARY Number of Participants by Dose for Ixabepilone/Paclitaxel |
145; 144; 139; 142; 130; 139 | — |
| SECONDARY Reason for First Dose Reduction of AC |
5; 7; 1; 3; 3; 3 | — |
| SECONDARY Reason for First Dose Reduction of Ixabepilone/Paclitaxel |
18; 18; 10; 3; 2; 0 | — |
| SECONDARY Number of Participants With Course Delay and Reason for Delay for AC |
41; 43; 5; 6; 6; 10 | — |
| SECONDARY Number of Participants With Dose Delay and Reason for Dose Delay for Ixabepilone/Paclitaxel |
31; 51; 3; 5; 6; 15 | — |
Eligibility Criteria
Inclusion criteria
- Histologically confirmed primary invasive adenocarcinoma of the breast , T2-3, N0-3, M0, with tumor size of ≥ 2 cm
- All patients with early stage breast adenocarcinoma may enroll irrespective of receptor status
- No prior treatment for breast cancer excluding therapy for DCIS
- Karnofsky performance status of 80 - 100
- left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multiple gated acquisition (MUGA)
- Adequate hematologic, hepatic and renal function
Exclusion Criteria
- women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy during and up to 8 weeks after the last dose of the investigational drug
- Women who are pregnant or breastfeeding
- Inflammatory or metastatic breast cancer
- Unfit for breast and/or axillary surgery
- Evidence of baseline sensory or motor neuropathy
- Significant history of cardiovascular disease, serious intercurrent illness or infections including known human immu immunodeficiency virus (HIV) infection
- History of prior anthracycline therapy Allergies to any study medication or Cremophor® EL
Data sourced from ClinicalTrials.gov (NCT00455533). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.