Nab-Paclitaxel in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This phase II trial studies the side effects of nab-paclitaxel in treating older patients with breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the tolerability (grade 2-5 toxicity, neuropathy grade 2 or higher, need for dose reductions, or delays) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer. SECONDARY OBJECTIVES: I. To evaluate the efficacy (response and time to progression) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer using a stratification factor based on patient age (at least 5 patients age 75 years or older and no more than 15 patients age 65-70 years). II. To explore predictors of the need for dose reduction, dose delays, or grade 2-5 toxicity and neuropathy grade 2 or higher based on a cancer-specific geriatric assessment. OUTLINE: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Official Title
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Efficacy and Tolerability of Nanoparticle Albumin Bound Paclitaxel (Abraxane) in Patients 65 and Older With Locally Advanced or Metastatic Breast Cancer

Conditions
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Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma, Recurrent Breast Carcinoma, Stage III Breast Cancer AJCC v7, Stage IIIA Breast Cancer AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Nab-paclitaxel
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic breast cancer Any estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2neu) status as long as the patient will receive nab-paclitaxel alone First or second line chemotherapy treatment for metastatic disease Karnofsky performance status (KPS) >= 70% Resolution of grade >= 2 toxicity from prior therapy (other than alopecia) Peripheral neuropathy =< grade 1 Absolute neutrophil count >= 1,500/mm^3 Platelets >= 100,000 cells/mm^3 Hemoglobin (Hb) >= 9.0 g/dl Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal Alkaline phosphatase =< 2.5 x upper limit of normal unless bone metastasis are present in the absence of liver metastases Bilirubin =< 1.5 mg/dl Creatinine clearance (calculated or 24 hour) >= 30 ml/min Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients may not be receiving any other investigational agents Untreated central nervous system (CNS) metastases or symptomatic CNS metastases requiring escalating doses of corticosteroids Known history of allergic reactions to paclitaxel Presence of any serious or uncontrolled infection Receipt of a taxane for adjuvant therapy or metastatic disease in the last 12 months

Ages Eligible for Study
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Minimum Age: 65 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: Treatment (nab-paclitaxel)<br>Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Nab-paclitaxel<br>* Given IV<br>* Other names: protein-bound paclitaxel;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 | Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to treatment. | During and after treatment, up to 2.5 years | 
| Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment | Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to treatment. | On treatment, 28 days per cycle up to 30 months | 
| Rate of Participants With a Dose Reduction | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. | On treatment, up to 30 months | 
| Rate of Participants Requiring Dose Holds | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. | While on treatment, up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Determined by Response Evaluation Criteria in Solid Tumors | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for objective response rate (complete response [CR] + partial response [PR]). RECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Additionally, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study | Up to 2.5 years | 
| Median Progression Free Survival (PFS) | PFS will be estimated using the product limit method of Kaplan and Meier. | From the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed for about 1.5 years | 
| Cancer-specific Geriatric (CARG) Assessment | General linear models and descriptive methods will be used to explore factors as identified by a CARG assessment that may be predictive of toxicity (grade 3 or higher adverse events) or dose reduction. The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxicity. Scores from 0 to 5 are considered low risk, 6 to 9 are considered intermediate risk, and 10 to 19 are considered high risk. | CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months |