Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer
Brief summary
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
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.
Interventions
DRUGpaclitaxel albumin-stabilized nanoparticle formulation
100 mg/m2 3 weeks on 1 week off
OTHERpharmacological study
Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 and 48 hours
OTHERphysiologic testing
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
OTHERquestionnaire administration
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
OTHERstudy of socioeconomic and demographic variables
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
PROCEDUREcognitive assessment
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
PROCEDUREpsychosocial assessment and care
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
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
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Curve Over 24 Hours (AUC24) | Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment | 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 |
| Mean Clearance (CL) | Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Up to 2.5 years | 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 |
| Best Response | Assessed after every 2 cycles of therapy until progression, up to 2.5 years | 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. |
| Median Event-free Survival (EFS) in Months | 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 | 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 |
| Number of Participants Requiring Dose Reductions | At the completion of treatment, up to 2.5 years | 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. |
| Number of Participants With a Dose Omission | At the completion of treatment, up to 2.5 years | 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. |
| Percent of Participants With a Grade 3 Toxicity | At the completion of treatment, up to 2.5 years | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMina Sedrak, MD
City of Hope Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nab-paclitaxel paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off
pharmacological study: Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 and 48 hours
physiologic testing: Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
questionnaire administration: Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
study of socioeconomic and demographic variables: Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
cognitive assessment: Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
psychosocial assessment and care: Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | Nab-paclitaxel |
|---|---|
| Age, Continuous | 60 years |
| Age, Customized <50 | 10 Participants |
| Age, Customized 50-59 | 5 Participants |
| Age, Customized 60-69 | 15 Participants |
| Age, Customized >=70 | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 30 Participants |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 26 / 39 |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 2 / 39 |
Outcome results
Primary
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
Time frame: Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
Population: Three participants did not have AUC data through 24 hours post treatment due to incomplete blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nab-paclitaxel | Mean Area Under the Curve Over 24 Hours (AUC24) | 4711 µg/mL*hour | Standard Deviation 2777 |
Comparison: Linear regression of ln AUC24 on age in yearsp-value: 0.055Regression, Linear
Comparison: Linear regression of ln AUC24 on chemotherapy toxicity risk scorep-value: 0.013Regression, Linear
Primary
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
Time frame: Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
Population: Nine participants did not have CL data due to incomplete blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nab-paclitaxel | Mean Clearance (CL) | 37.16 L/h | Standard Deviation 14.81 |
Comparison: Linear regression of ln CL on age in yearsp-value: 0.25Regression, Linear
Comparison: Linear regression of ln CL versus chemotherapy toxicity risk scorep-value: 0.04Regression, Linear
Secondary
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.
Time frame: Assessed after every 2 cycles of therapy until progression, up to 2.5 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-paclitaxel | Best Response | Partial Remission | 12 Participants |
| Nab-paclitaxel | Best Response | Stable Disease | 15 Participants |
| Nab-paclitaxel | Best Response | Progressive Disease | 10 Participants |
| Nab-paclitaxel | Best Response | Not evaluable | 2 Participants |
Secondary
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
Time frame: Up to 2.5 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Low risk score : Grade 3 toxicity | 5 Participants |
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Low risk score : No grade 3 toxicity | 25 Participants |
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Medium risk score : Grade 3 toxicity | 3 Participants |
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | Medium risk score : No grade 3 toxicity | 3 Participants |
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | High risk score : Grade 3 toxicity | 2 Participants |
| Nab-paclitaxel | Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score | High risk score : No grade 3 toxicity | 1 Participants |
p-value: 0.041Fisher Exact
Secondary
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
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-paclitaxel | Median Event-free Survival (EFS) in Months | 5.7 months |
Secondary
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.
Time frame: At the completion of treatment, up to 2.5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nab-paclitaxel | Number of Participants Requiring Dose Reductions | 11 Participants |
Comparison: Difference in age based on whether there was need for a dose reduction.p-value: 0.3895% CI: [-16.5, 6.7]t-test, 2 sided
Comparison: Difference in AUC24 based on the need of a dose reduction.p-value: 0.7695% CI: [-0.33, 0.44]t-test, 2 sided
Comparison: Difference in clearance based on whether there was a need for dose reduction.p-value: 0.7595% CI: [-0.49, 0.36]t-test, 2 sided
Secondary
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.
Time frame: At the completion of treatment, up to 2.5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nab-paclitaxel | Number of Participants With a Dose Omission | 15 Participants |
Comparison: Difference in age based on whether there was need for a dose omission.p-value: 0.1595% CI: [-2.3, 13.9]t-test, 2 sided
Comparison: Difference in AUC24 based on whether there was need for a dose omission.p-value: 0.6195% CI: [-0.39, 0.23]t-test, 2 sided
Comparison: Difference in clearance based on whether there was a need for a dose omission.p-value: 0.5195% CI: [-0.22, 0.42]t-test, 2 sided
Secondary
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.
Time frame: At the completion of treatment, up to 2.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nab-paclitaxel | Percent of Participants With a Grade 3 Toxicity | 26 percentage of participants |
Comparison: Difference in age based on whether a participant experienced grade 3 toxicity.p-value: 0.7595% CI: [-9.3, 12.7]t-test, 2 sided
Comparison: Difference in AUC based on whether a participant experienced grade 3 toxicity.p-value: 0.1395% CI: [-0.12, 0.81]t-test, 2 sided
Comparison: Difference in clearance based on whether a participant experienced grade 3 toxicity.p-value: 0.3495% CI: [-0.67, 0.25]t-test, 2 sided