Phase II Trial Comparing ABI-007 (Abraxane®, Nab®-Paclitaxel) to Taxotere in First Line Therapy of Patients With Stage IV Breast Cancer

Study Overview
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Brief Summary
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This was an open-label study conducted comparing the toxicity and antitumor activity of ABI-007 (Abraxane®, nab®-paclitaxel) to docetaxel (Taxotere).

Detailed Description
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This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity: the maximum tolerated dose (MTD) of ABI-007 300 mg/m^2 every 3 weeks; ABI-007 100 mg/m^2 administered weekly for 3 weeks with a 1 week rest; ABI-007 150 mg/m^2 administered weekly for 3 weeks with a 1 week rest; the standard dose and schedule of Taxotere (100 mg/m^2 every 3 weeks).

Official Title
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A Randomized Phase II Study of Weekly or Every 3 Weeks ABI-007 Versus Every 3 Weeks Taxotere as First Line Therapy of Stage IV (Metastatic) Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: ABI-007
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients had to meet the following criteria to be eligible for the study: Pathologically confirmed adenocarcinoma of the breast. No prior chemotherapy for metastatic breast cancer. Stage IV disease. Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm). At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy. At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal. At least 4 weeks since major surgery, with full recovery. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Age ≥18 years. Patient had the following blood counts at Baseline: Absolute neutrophil count (ANC) ≥1.5*10^9 cells/L Platelets ≥100*10^9 cells/L Hemoglobin (Hgb) ≥9 g/dL. Patient had the following baseline blood chemistry levels: Aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT])≥2.5x upper limit of normal (ULN) range Total bilirubin normal Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis) Creatinine ≥1.5 mg/dL. Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug). If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study. Informed consent had been obtained. Exclusion Criteria: Patients who met any of the following criteria were excluded from the study: Prior neo-adjuvant or adjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen. Cumulative life-time dose of doxorubicin >360 mg/m^2. Doxorubicin was allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease. Concurrent immunotherapy or hormonal therapy for breast cancer. Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment. Serious intercurrent medical or psychiatric illness, including serious active infection. History of class II-IV congestive heart failure. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer. Patients who had received an investigational drug within the previous 3 weeks. Patient was enrolled in a different clinical study in which investigational procedures were performed or investigational therapies were administered. Also, a patient was not permitted enroll in such clinical trials while participating in this study. Pregnant or nursing women Patients with prior hypersensitivity to either Taxol or Taxotere.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-007 300 mg/m^2 q3w<br>ABI-007 300 mg/m^2 administered once every third week (q3w). | Drug: ABI-007<br>* ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.<br>* Other names: nab®-paclitaxel;|
| Experimental: ABI-007 100 mg/m^2 weekly<br>ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest | Drug: ABI-007<br>* ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.<br>* Other names: nab®-paclitaxel;|
| Experimental: ABI-007 150 mg/m^2 weekly<br>ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest | Drug: ABI-007<br>* ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.<br>* Other names: nab®-paclitaxel;|
| Active Comparator: Docetaxel 100 mg/m^2, q3w<br>Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). | Drug: Docetaxel<br>* Docetaxel dosed q3w at 100 mg/m^2<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR. | Day 1 up to 95 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately | Day 1 up to 95 weeks | 
| Kaplan-Meier Estimates for Progression-free Survival (PFS) | PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. | Day 1 up to 95 weeks | 
| Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Day 1 - 95 weeks | 
| Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Day 1 - 95 weeks | 
| Kaplan-Meier Estimate for Overall Survival (OS) | Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010). | Day 1 to 221 weeks | 
| Participants With Treatment-Emergent, Treatment-Related Adverse Events | Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death. | Day 1 up to 125 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer, nab paclitaxel, docetaxel,