Multicenter Study of Pharmacokinetic-Guided Docetaxel in Breast Cancer Patients Receiving Docetaxel and Cyclophosphamide

Study Overview
=================
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.

Official Title
-----------------
Multicenter Study Investigating Utilization of Pharmacokinetic(PK)-Guided Docetaxel in Senior Adult Breast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) Chemotherapy

Conditions
-----------------
Breast Cancer, Breast Cancer Female

Intervention / Treatment
-----------------
* Drug: Standard of Care: Docetaxel
* Drug: Standard of Care: Cyclophosphamide
* Other: Function Assessment of Cancer Therapy (FACT) Surveys


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of Care + Surveys<br>Standard of Care Docetaxel and Cyclophosphamide (TC) Chemotherapy + Surveys. TC Regimen with Function Assessment of Cancer Therapy (FACT) Surveys. All participants will receive TC for cycle 1 with subsequent cycles repeated every 3 weeks for a total of 4 cycles. All initial dosing will be based on actual body weight and height. Participants will receive up to 4 doses of chemotherapy. Following their 4th dose of chemotherapy, or the last dose of chemotherapy in which blood level monitoring was performed, participants will be assessed for side effects from the chemotherapy and complete their final written 53 question survey about their quality of life. | Drug: Standard of Care: Docetaxel<br>* 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.<br>* Other names: Taxotere®;Drug: Standard of Care: Cyclophosphamide<br>* 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.<br>* Other names: Cytoxan®;Other: Function Assessment of Cancer Therapy (FACT) Surveys<br>* 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.<br>* Other names: Questionnaire;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Cycle 4 - Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 6 months | 
| 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). | Baseline and Post Cycle 1 | 
| 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). | Baseline and Post Cycle 1 | 
| 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. | Baseline and Post Cycle 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
senior adult, postmenopausal