Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma, Recurrent Breast Carcinoma, Stage IIIA Breast Cancer AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage III Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7
Conditions
Brief summary
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
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGNab-paclitaxel
Given IV
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 | During and after treatment, up to 2.5 years | 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. |
| Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment | On treatment, 28 days per cycle up to 30 months | 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. |
| Rate of Participants With a Dose Reduction | On treatment, up to 30 months | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. |
| Rate of Participants Requiring Dose Holds | While on treatment, up to 30 months | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Determined by Response Evaluation Criteria in Solid Tumors | Up to 2.5 years | 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 |
| Median Progression Free Survival (PFS) | 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 | PFS will be estimated using the product limit method of Kaplan and Meier. |
| Cancer-specific Geriatric (CARG) Assessment | CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMina Sedrak
City of Hope Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Nab-paclitaxel) 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.
Laboratory Biomarker Analysis: Correlative studies
Nab-paclitaxel: Given IV
Questionnaire Administration: Ancillary studies | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Treatment (Nab-paclitaxel) |
|---|---|
| Age, Continuous | 73 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Receptor status HR-positive | 30 Participants |
| Receptor status Triple-negative | 10 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 35 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 14 / 40 |
Outcome results
Primary
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.
Time frame: During and after treatment, up to 2.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Nab-paclitaxel) | Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 | 90 percentage of participants |
Primary
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.
Time frame: On treatment, 28 days per cycle up to 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Nab-paclitaxel) | Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment | 58 percentage of participants |
Primary
Rate of Participants Requiring Dose Holds
Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.
Time frame: While on treatment, up to 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Nab-paclitaxel) | Rate of Participants Requiring Dose Holds | 75 percentage of participants |
Primary
Rate of Participants With a Dose Reduction
Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.
Time frame: On treatment, up to 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Nab-paclitaxel) | Rate of Participants With a Dose Reduction | 50 percentage of participants |
Secondary
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.
Time frame: CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Nab-paclitaxel) | Cancer-specific Geriatric (CARG) Assessment | Low CARG chemotherapy toxicity risk | 21 Participants |
| Treatment (Nab-paclitaxel) | Cancer-specific Geriatric (CARG) Assessment | Intermediate CARG chemotherapy toxicity risk | 15 Participants |
| Treatment (Nab-paclitaxel) | Cancer-specific Geriatric (CARG) Assessment | High CARG chemotherapy toxicity risk | 4 Participants |
Comparison: CARG chemotherapy toxicity risk predictive of chemotherapy toxicity (grade 3)p-value: 0.0195% CI: [1.3, 33.1]Fisher Exact
Comparison: CARG chemotherapy toxicity risk predictive of dose reduction due to chemotherapy toxicityp-value: 0.0295% CI: [1.04, 1.8]t-test, 2 sided
Secondary
Median Progression Free Survival (PFS)
PFS will be estimated using the product limit method of Kaplan and Meier.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Nab-paclitaxel) | Median Progression Free Survival (PFS) | 6.5 months |
Secondary
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
Time frame: Up to 2.5 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Nab-paclitaxel) | Response Determined by Response Evaluation Criteria in Solid Tumors | Complete remission | 1 Participants |
| Treatment (Nab-paclitaxel) | Response Determined by Response Evaluation Criteria in Solid Tumors | Partial remission | 13 Participants |
| Treatment (Nab-paclitaxel) | Response Determined by Response Evaluation Criteria in Solid Tumors | Stable disease | 16 Participants |
| Treatment (Nab-paclitaxel) | Response Determined by Response Evaluation Criteria in Solid Tumors | Progressive disease | 4 Participants |
| Treatment (Nab-paclitaxel) | Response Determined by Response Evaluation Criteria in Solid Tumors | Off treatment prior to disease assessment | 6 Participants |
95% CI: [21, 52]