Clinical trial NCT00609791: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage IV breast cancer
male breast cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Area Under the Curve Over 24 Hours (AUC24)
timeFrame: Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
measure: Mean Clearance (CL)
timeFrame: Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment
Secondary outcomes:
measure: Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score
timeFrame: Up to 2.5 years
measure: Best Response
timeFrame: Assessed after every 2 cycles of therapy until progression, up to 2.5 years
measure: Median Event-free Survival (EFS) in Months
timeFrame: 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
measure: Number of Participants Requiring Dose Reductions
timeFrame: At the completion of treatment, up to 2.5 years
measure: Number of Participants With a Dose Omission
timeFrame: At the completion of treatment, up to 2.5 years
measure: Percent of Participants With a Grade 3 Toxicity
timeFrame: At the completion of treatment, up to 2.5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Pasadena
country: United States
facility: City of Hope Medical Group
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Mina Sedrak, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.