Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients of Different Ages With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Age-Related Changes in Nanoparticle Albumin Bound (Nab) Paclitaxel Pharmacokinetics and Pharmacodynamics

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00609791
• Other study ID #: 07157
• Secondary ID: P30CA033572CHNMC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 11, 2008
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 30, 2024
• Est. primary completion date: October 25, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• paclitaxel albumin-stabilized nanoparticle formulation
100 mg/m2 3 weeks on 1 week off

Other:
• 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

Procedure:
• 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

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
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	Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
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	Up to 2.5 years
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.	Assessed after every 2 cycles of therapy until progression, up to 2.5 years
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	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
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.	At the completion of treatment, up to 2.5 years
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.	At the completion of treatment, up to 2.5 years
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.	At the completion of treatment, up to 2.5 years