Back to resultsPaclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients of Different Ages With Metastatic Breast Cancer
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
paclitaxel albumin-stabilized nanoparticle formulation
pharmacological study
physiologic testing
questionnaire administration
study of socioeconomic and demographic variables
cognitive assessment
psychosocial assessment and care
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring recurrent breast cancer, stage IV breast cancer, male breast cancer
Eligibility 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
Sites / Locations
- City of Hope Medical Center
- City of Hope Medical Group
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
nab-paclitaxel
Arm Description
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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
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.
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
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.
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.
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.
Full Information
NCT ID
NCT00609791
First Posted
February 6, 2008
Last Updated
August 7, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00609791
Brief Title
Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients of Different Ages With Metastatic Breast Cancer
Official Title
Age-Related Changes in Nanoparticle Albumin Bound (Nab) Paclitaxel Pharmacokinetics and Pharmacodynamics
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 11, 2008 (Actual)
Primary Completion Date
October 25, 2011 (Actual)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
nab-paclitaxel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
paclitaxel albumin-stabilized nanoparticle formulation
Intervention Description
100 mg/m2 3 weeks on 1 week off
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 and 48 hours
Intervention Type
Other
Intervention Name(s)
physiologic testing
Intervention Description
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
Intervention Type
Other
Intervention Name(s)
study of socioeconomic and demographic variables
Intervention Description
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
Intervention Type
Procedure
Intervention Name(s)
cognitive assessment
Intervention Description
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
Intervention Type
Procedure
Intervention Name(s)
psychosocial assessment and care
Intervention Description
Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy
Primary Outcome Measure Information:
Title
Mean Area Under the Curve Over 24 Hours (AUC24)
Description
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
Title
Mean Clearance (CL)
Description
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
Secondary Outcome Measure Information:
Title
Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score
Description
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
Title
Best Response
Description
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
Title
Median Event-free Survival (EFS) in Months
Description
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
Title
Number of Participants Requiring Dose Reductions
Description
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
Title
Number of Participants With a Dose Omission
Description
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
Title
Percent of Participants With a Grade 3 Toxicity
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mina Sedrak, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
City of Hope Medical Group
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25492923
Citation
Hurria A, Blanchard MS, Synold TW, Mortimer J, Chung CT, Luu T, Katheria V, Rotter AJ, Wong C, Choi A, Feng T, Ramani R, Doan CM, Brown J, Somlo G. Age-related changes in nanoparticle albumin-bound paclitaxel pharmacokinetics and pharmacodynamics: influence of chronological versus functional age. Oncologist. 2015 Jan;20(1):37-44. doi: 10.1634/theoncologist.2014-0202. Epub 2014 Dec 9.
Results Reference
derived
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Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients of Different Ages With Metastatic Breast Cancer
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