Breast Cancer, Breast Cancer Female
Conditions
Keywords
senior adult, postmenopausal
Brief summary
The purpose of this study is to adjust the amount of docetaxel participants receive based on the level of docetaxel measured in their blood. This method of dose adjustment is called pharmacokinetic (PK)-adjusted docetaxel. The researchers believe that adjusting the dose of docetaxel using this method will lessen the side effects associated with docetaxel in cancer treatment.
Interventions
DRUGStandard of Care: Docetaxel
Pharmacokinetic(PK)-guided docetaxel. Cycle 1: 75 mg/m\^2, intravenously (IV) on Day 1 for 60 minutes. Beginning with cycle 2, the docetaxel dose will be individually adjusted before each cycle.
DRUGStandard of Care: Cyclophosphamide
Cycle 1: 600 mg/m\^2, via IV on Day 1 for 30 minutes. The cyclophosphamide dose will not be changed unless dictated by toxicity.
OTHERFunction Assessment of Cancer Therapy (FACT) Surveys
Participants will complete the FACT-Taxane and FACT-Breast quality of life assessment written surveys at baseline, during each chemotherapy cycle, and 3-5 weeks following the last cycle in which PK monitoring was performed.
Sponsors
Saladax Biomedical, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have histologically confirmed localized or locally advanced breast cancer for which the treatment plan includes chemotherapy with 4 cycles of standard TC (docetaxel 75 mg/m\^2 and cyclophosphamide 600mg/m\^2) * Age \>/= 65 years (Senior adult focused study given increased risk for toxicity) * Participants must be female * Eastern Cooperative Oncology Group (ECOG) performance status \<2 * Must have normal organ and marrow function * No pre-existing neuropathy grade \> 1 per the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 * Be postmenopausal (defined as amenorrheic for at least 12 months) * Must be informed of the investigational nature of this study and be willing to provide written informed consent in accordance with Institutional guidelines and Good Clinical Practice (GCP) indicating that they understand the purpose of and procedures required for the study and are willing to participate prior to the beginning of any specific study procedures.
Exclusion criteria
* Have uncontrolled illness (including, but not limited to, ongoing or active infection, congestive heart failure, angina pectoris, or cardiac arrhythmia) that would limit compliance with study requirements * Have psychiatric illness that would limit compliance with study requirements * Have history of allergic reactions attributed to compounds of similar chemical or biologic composition to taxanes (docetaxel or paclitaxel) or cyclophosphamide * Have known seropositivity for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen, or syphilis. Does not require serologic confirmation as a study procedure. * Not willing to follow protocol requirements or to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Achieving Targeted Area Under the Curve (AUC) | Cycle 4 - Up to 6 months | Rate of PK guided dosing of docetaxel chemotherapy improving the ability to achieve a targeted AUC ( 2.5-3.7 mg\*hr/L) within 4 cycles of therapy in patients \> 65 years of age with breast cancer receiving TC (docetaxel and cyclophosphamide) as compared with historical non-PK guided therapy from patients receiving a similar regimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia | Up to 6 months | The incidence of grade 3 and 4 neutropenia and febrile neutropenia in cycles following PK adjustment (cycles 2-4) will be compared with cycle 1 and historical non-PK guided therapy using the Wilcoxon-Rank sum assessment. |
| Association Between Scores - Chemotherapy Risk Assessment Scale for High-Age Patients | Baseline and Post Cycle 1 | The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score will be reported as ordinal data (low, intermediate-low, intermediate-high, or high risk). |
| Association Between Scores - Instrumental Activities of Daily Living | Baseline and Post Cycle 1 | The Instrumental Activities of Daily Living (IADL) total score will be reported as binomial data (greater or less than 26 based on how it is incorporated into the CRASH score). |
| Association Between Scores - Cumulative Illness Rating Scale for Geriatrics | Baseline and Post Cycle 1 | The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) will be reported as discrete data out of a possible score of 65. The Wilcoxon-Rank sum and Chi-squared tests will be used as appropriate. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Patient Profiles and Function Assessment of Cancer Therapy (FACT) Scores | Up to 6 months | The relationship between PK-guided docetaxel patient PK profiles and the Function Assessment of Cancer Therapy (FACT) Taxane and Breast Cancer scores will be described. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at Moffitt Cancer Center, February 2016 through June 2017.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care + Surveys Standard of Care Docetaxel and Cyclophosphamide (TC) Chemotherapy + Surveys. TC Regimen with Function Assessment of Cancer Therapy (FACT) Surveys. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Standard of Care + Surveys |
|---|---|
| Age, Continuous | 72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 9 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
Rate of Achieving Targeted Area Under the Curve (AUC)
Rate of PK guided dosing of docetaxel chemotherapy improving the ability to achieve a targeted AUC ( 2.5-3.7 mg\*hr/L) within 4 cycles of therapy in patients \> 65 years of age with breast cancer receiving TC (docetaxel and cyclophosphamide) as compared with historical non-PK guided therapy from patients receiving a similar regimen.
Time frame: Cycle 4 - Up to 6 months
Population: All participants evaluable at time of analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care + Surveys | Rate of Achieving Targeted Area Under the Curve (AUC) | AUC mg*hr/L: 2.5-3.7 | 5 Participants |
| Standard of Care + Surveys | Rate of Achieving Targeted Area Under the Curve (AUC) | AUC mg*hr/L: <2.5 | 3 Participants |
Secondary
Association Between Scores - Chemotherapy Risk Assessment Scale for High-Age Patients
The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score will be reported as ordinal data (low, intermediate-low, intermediate-high, or high risk).
Time frame: Baseline and Post Cycle 1
Population: Descriptive analysis was planned for 52 participants. Due to the small number of participants enrolled, analyzing additional correlations was not possible.
Secondary
Association Between Scores - Cumulative Illness Rating Scale for Geriatrics
The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) will be reported as discrete data out of a possible score of 65. The Wilcoxon-Rank sum and Chi-squared tests will be used as appropriate.
Time frame: Baseline and Post Cycle 1
Population: Descriptive analysis was planned for 52 participants. Due to the small number of participants enrolled, analyzing additional correlations was not possible.
Secondary
Association Between Scores - Instrumental Activities of Daily Living
The Instrumental Activities of Daily Living (IADL) total score will be reported as binomial data (greater or less than 26 based on how it is incorporated into the CRASH score).
Time frame: Baseline and Post Cycle 1
Population: Descriptive analysis was planned for 52 participants. Due to the small number of participants enrolled, analyzing additional correlations was not possible.
Secondary
Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia
The incidence of grade 3 and 4 neutropenia and febrile neutropenia in cycles following PK adjustment (cycles 2-4) will be compared with cycle 1 and historical non-PK guided therapy using the Wilcoxon-Rank sum assessment.
Time frame: Up to 6 months
Population: All participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care + Surveys | Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia | Participants with Grade 3 or 4 neutropenia | 2 Participants |
| Standard of Care + Surveys | Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia | Participants with Febrile neutropenia | 0 Participants |
Other Pre-specified
Comparison of Patient Profiles and Function Assessment of Cancer Therapy (FACT) Scores
The relationship between PK-guided docetaxel patient PK profiles and the Function Assessment of Cancer Therapy (FACT) Taxane and Breast Cancer scores will be described.
Time frame: Up to 6 months
Population: Descriptive analysis was planned for 52 participants. Due to the small number of participants enrolled, analyzing additional correlations was not possible.