Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients of Different Ages With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Gathering information from patients of different ages receiving paclitaxel albumin-stabilized nanoparticle formulation for metastatic breast cancer may help doctors understand how the age of the patient changes the way the drug works. PURPOSE: This phase II trial is studying how well paclitaxel albumin-stabilized nanoparticle formulation works in treating patients of different ages with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine age-related changes in the pharmacokinetics (pK) of weekly paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) in patients with metastatic breast cancer. To determine age-related changes in the pharmacodynamics (toxicity) of nab-paclitaxel in these patients. Secondary To determine response and time to progression in these patients. To explore predictors of pK parameters in these patients. To explore predictors of the need for dose reduction, dose delays, or grade 3 or 4 toxicity in these patients. OUTLINE: Patients are stratified by age in years (< 50 vs 50-60 vs 60-70 vs > 70). Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once daily on days 1, 8, and 15 as planned. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Blood is drawn for pharmacokinetic studies periodically during course 1. Patients complete questionnaires regarding risk factors that would predict for pharmacokinetic parameters at baseline, prior to the third course of treatment, and at end of study. Data collected include medical characteristics, demographics, functional status, comorbidity, psychological status, social functioning and support, nutritional status, and cognition.

Official Title
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Age-Related Changes in Nanoparticle Albumin Bound (Nab) Paclitaxel Pharmacokinetics and Pharmacodynamics

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: paclitaxel albumin-stabilized nanoparticle formulation
* Other: pharmacological study
* Other: physiologic testing
* Other: questionnaire administration
* Other: study of socioeconomic and demographic variables
* Procedure: cognitive assessment
* Procedure: psychosocial assessment and care


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Diagnosis of metastatic breast cancer Any estrogen receptor, progesterone receptor, or HER-2/neu status allowed as long as the patient will receive paclitaxel albumin-stabilized nanoparticle formulation alone First- or second-line chemotherapy treatment for metastatic disease planned Exclusion criteria: Untreated CNS metastases or symptomatic CNS metastases requiring escalating doses of corticosteroids PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% WBC ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastases are present in the absence of liver metastases) Bilirubin ≤ 1.5 mg/dL Peripheral neuropathy ≤ grade 1 Creatinine clearance ≥ 30 mL/min (calculated or 24-hour) Negative pregnancy test Fertile patients must use effective contraception Not pregnant or nursing No known history of allergic reactions to paclitaxel No serious or uncontrolled infection Ability to understand and the willingness to sign a written informed consent document PRIOR CONCURRENT THERAPY: See Disease Characteristics No ≥ grade 2 toxicity from prior therapy (other than alopecia) No taxane for adjuvant therapy or metastatic disease within the past 12 months No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-paclitaxel<br> | Drug: paclitaxel albumin-stabilized nanoparticle formulation<br>* 100 mg/m2 3 weeks on 1 week off<br>Other: pharmacological study<br>* Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 and 48 hours<br>Other: physiologic testing<br>* Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy<br>Other: questionnaire administration<br>* Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy<br>Other: study of socioeconomic and demographic variables<br>* Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy<br>Procedure: cognitive assessment<br>* Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy<br>Procedure: psychosocial assessment and care<br>* Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Area Under the Curve Over 24 Hours (AUC24) | Mean of area under the curve over 24 hours (AUC24) reported as well as linear regression of AUC24 by age and chemotherapy toxicity risk score. Chemotherapy toxicity risk score is based on the following variables and the value assigned to them. Higher scores indicate more risk, range of 2-19: patient age (>=72 years); creatinine clearance (<34 mL/min); presence of amenia (<10 g/dL); hearing impairment; falls in the last 6 months; need for assistance with taking medications; limitations in walking one block; decreased social activities; chemotherapy dosing; number of chemotherapy drugs; cancer type | Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment | 
| Mean Clearance (CL) | Mean CL reported as well as regression results of CL by age and chemotherapy toxicity risk score. Chemotherapy toxicity risk score is based on the following variables and the value assigned to them. Higher scores indicate more risk, range of 2-19: patient age (>=72 years); creatinine clearance (<34 mL/min); presence of amenia (<10 g/dL); hearing impairment; falls in the last 6 months; need for assistance with taking medications; limitations in walking one block; decreased social activities; chemotherapy dosing; number of chemotherapy drugs; cancer type | Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Comparison of presence of grade 3 toxicity rate by risk score distribution. Chemotherapy toxicity risk score is based on the following variables. Higher scores indicate more risk, range of 2-19: patient age (>=72 years); creatinine clearance (<34 mL/min); presence of amenia (<10 g/dL); hearing impairment; falls in the last 6 months; need for assistance with taking medications; limitations in walking one block; decreased social activities; chemotherapy dosing; number of chemotherapy drugs; cancer type Chemotherapy toxicity risk score category: Low risk score - toxicity risk score: 0-5 Medium risk score - toxicity risk score: 6-9 High risk score - toxicity risk score: 10-19 | Up to 2.5 years | 
| Best Response | Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Assessed after every 2 cycles of therapy until progression, up to 2.5 years | 
| Median Event-free Survival (EFS) in Months | Median and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for EFS. EFS will be estimated using the product limit method of Kaplan and Meier. EFS is defined by time to disease recurrence, disease progression or death to due to any cause | From the date treatment begins until the first date on which recurrence, progression or death due to any cause, assessed up to 3.5 years | 
| Number of Participants Requiring Dose Reductions | Number of participants requiring a dose reduction is reported and analysis was performed using a student's 2 sample t test to determine the need of dose reductions based on age, AUC, and CL. | At the completion of treatment, up to 2.5 years | 
| Number of Participants With a Dose Omission | Number of participants with a dose omission is reported and analysis was performed using a student's 2 sample t test to determine the need of dose omission based on age, AUC, and CL. | At the completion of treatment, up to 2.5 years | 
| Percent of Participants With a Grade 3 Toxicity | Percent of participants experiencing a grade 3 toxicity is reported and analysis was performed using a student's 2 sample t test to determine the presence of grade 3 toxicity based on age, AUC, and CL. | At the completion of treatment, up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, male breast cancer