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

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00609791
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 40
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 178.4
• Patients Per Site: 20
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: paclitaxel albumin-stabilized nanoparticle formulation; Other: pharmacological study; Other: physiologic testing; Other: questionnaire administration; Other: study of socioeconomic and demographic variables; Procedure: cognitive assessment; Procedure: psychosocial assessment and care	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Age-Related Changes in Nanoparticle Albumin Bound (Nab) Paclitaxel Pharmacokinetics and Pharmacodynamics
• Actual Study Start Date: Feb 11, 2008
• Actual Primary Completion Date: Oct 25, 2011
• Anticipated Study Completion Date: Dec 25, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: nab-paclitaxel

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; Other: physiologic testing; Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy; Other: questionnaire administration; Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy; Other: 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; Procedure: psychosocial assessment and care; Prior to treatment, at the end of 2 cycles of therapy and upon completion of therapy

Outcome Measures

Primary Outcome Measures

1. Mean Area Under the Curve Over 24 Hours (AUC24) [Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment]

   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

2. Mean Clearance (CL) [Cycle 1, week 1 at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post treatment]

   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

1. Grade 3 Toxicity Rate by Chemotherapy Toxicity Risk Score [Up to 2.5 years]

   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

2. Best Response [Assessed after every 2 cycles of therapy until progression, up to 2.5 years]

   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.

3. Median Event-free Survival (EFS) in Months [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]

   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

4. Number of Participants Requiring Dose Reductions [At the completion of treatment, up to 2.5 years]

   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.

5. Number of Participants With a Dose Omission [At the completion of treatment, up to 2.5 years]

   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.

6. Percent of Participants With a Grade 3 Toxicity [At the completion of treatment, up to 2.5 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010-3000
2	City of Hope Medical Group	Pasadena	California	United States	91105

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mina Sedrak, MD, City of Hope Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 22, 2019

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT00609791
• Other Study ID Numbers: 07157; P30CA033572; CHNMC-07157; ABRAXIS-ABX206-BC07US; CDR0000586461; NCI-2011-02403
• First Posted: Feb 7, 2008
• Last Update Posted: Aug 9, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by City of Hope Medical Center: recurrent breast cancer; stage IV breast cancer; male breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Period Title: Overall Study
STARTED	40
COMPLETED	39
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Age, Customized (Count of Participants)
<50	10 25.6%
50-59	5 12.8%
60-69	15 38.5%
>=70	9 23.1%
Sex: Female, Male (Count of Participants)
Female	39 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 20.5%
Not Hispanic or Latino	31 79.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	7 17.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5.1%
White	30 76.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Three participants did not have AUC data through 24 hours post treatment due to incomplete blood samples

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	36
Mean (Standard Deviation) [µg/mL*hour]	4711 (2777)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Linear regression of ln AUC24 on age in years
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.011
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0057
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Linear regression of ln AUC24 on chemotherapy toxicity risk score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.17
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Nine participants did not have CL data due to incomplete blood samples

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	30
Mean (Standard Deviation) [L/h]	37.16 (14.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Linear regression of ln CL on age in years
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.0074
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0063
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Linear regression of ln CL versus chemotherapy toxicity risk score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Low risk score : Grade 3 toxicity	5 12.8%
Low risk score : No grade 3 toxicity	25 64.1%
Medium risk score : Grade 3 toxicity	3 7.7%
Medium risk score : No grade 3 toxicity	3 7.7%
High risk score : Grade 3 toxicity	2 5.1%
High risk score : No grade 3 toxicity	1 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Partial Remission	12 30.8%
Stable Disease	15 38.5%
Progressive Disease	10 25.6%
Not evaluable	2 5.1%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Median (95% Confidence Interval) [months]	5.7

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Count of Participants [Participants]	11 28.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in age based on whether there was need for a dose reduction.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.38
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.89
	Confidence Interval	(2-Sided) 95%; -16.5 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in AUC24 based on the need of a dose reduction.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.058
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in clearance based on whether there was a need for dose reduction.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.063
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Count of Participants [Participants]	15 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in age based on whether there was need for a dose omission.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.81
	Confidence Interval	(2-Sided) 95%; -2.3 to 13.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in AUC24 based on whether there was need for a dose omission.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.079
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in clearance based on whether there was a need for a dose omission.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	26 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in age based on whether a participant experienced grade 3 toxicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95%; -9.3 to 12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in AUC based on whether a participant experienced grade 3 toxicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nab-paclitaxel
	Comments	Difference in clearance based on whether a participant experienced grade 3 toxicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.67 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 3.5 years
Arm/Group Title	Nab-paclitaxel
Arm/Group Description	paclitaxel albumin-stabilized nanoparticle formulation: 100 mg/m2 3 weeks on 1 week off 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 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
All Cause Mortality
	Nab-paclitaxel
	Affected / at Risk (%)	# Events
Total	26/39 (66.7%)
Serious Adverse Events
	Nab-paclitaxel
	Affected / at Risk (%)	# Events
Total	2/39 (5.1%)
Infections and infestations
Urinary tract infection	1/39 (2.6%)
Skin infection	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Nab-paclitaxel
	Affected / at Risk (%)	# Events
Total	39/39 (100%)
Blood and lymphatic system disorders
Lymph node pain	1/39 (2.6%)
Cardiac disorders
Atrial fibrillation	1/39 (2.6%)
Palpitations	1/39 (2.6%)
Sinus bradycardia	1/39 (2.6%)
Sinus tachycardia	1/39 (2.6%)
Hypertension	8/39 (20.5%)
Chest pain	4/39 (10.3%)
Ear and labyrinth disorders
Tinnitus	1/39 (2.6%)
Ear pain	1/39 (2.6%)
External ear pain	1/39 (2.6%)
Endocrine disorders
Hypothyroidism	1/39 (2.6%)
Eye disorders
Dry eye syndrome	5/39 (12.8%)
Eyelid function disorder	1/39 (2.6%)
Vision blurred	1/39 (2.6%)
Watering eyes	3/39 (7.7%)
Gastrointestinal disorders
Ascites	1/39 (2.6%)
Constipation	8/39 (20.5%)
Diarrhea	11/39 (28.2%)
Dry mouth	1/39 (2.6%)
Dyspepsia	3/39 (7.7%)
Enteritis	1/39 (2.6%)
Flatulence	1/39 (2.6%)
Gastric ulcer	1/39 (2.6%)
Hemorrhoids	1/39 (2.6%)
Nausea	15/39 (38.5%)
Mucositis	2/39 (5.1%)
Typhlitis	1/39 (2.6%)
Vomiting	7/39 (17.9%)
Hemorrhage	3/39 (7.7%)
Lower gastrointestinal hemorrhage	1/39 (2.6%)
Abdominal pain	10/39 (25.6%)
Peritoneal pain	1/39 (2.6%)
Stomach pain	1/39 (2.6%)
General disorders
Edema	1/39 (2.6%)
Chills	1/39 (2.6%)
Fatigue	27/39 (69.2%)
Fever	3/39 (7.7%)
Injection site reaction	1/39 (2.6%)
Edema limbs	11/39 (28.2%)
Localized edema	3/39 (7.7%)
Facial pain	1/39 (2.6%)
Hepatobiliary disorders
Hepatobiliary disease	1/39 (2.6%)
Immune system disorders
Allergic rhinitis	4/39 (10.3%)
Hypersensitivity	1/39 (2.6%)
Immune system disorder	1/39 (2.6%)
Infections and infestations
Bladder infection	2/39 (5.1%)
Catheter related infection	1/39 (2.6%)
Gingival infection	1/39 (2.6%)
Infection	1/39 (2.6%)
Infectious colitis	1/39 (2.6%)
Pharyngitis	1/39 (2.6%)
Scrotal infection	1/39 (2.6%)
Sinusitis	4/39 (10.3%)
Skin infection	1/39 (2.6%)
Small intestine infection	1/39 (2.6%)
Upper aerodigestive tract infection	1/39 (2.6%)
Upper respiratory infection	8/39 (20.5%)
Urinary tract infection	4/39 (10.3%)
Infection without neutropenia	1/39 (2.6%)
Injury, poisoning and procedural complications
Fracture	1/39 (2.6%)
Investigations
Hemoglobin decreased	36/39 (92.3%)
Leukocyte count decreased	27/39 (69.2%)
Lymphocyte count decreased	15/39 (38.5%)
Neutrophil count decreased	19/39 (48.7%)
Platelet count decreased	7/39 (17.9%)
Activated partial thromboplastin time prolonged	1/39 (2.6%)
Weight gain	1/39 (2.6%)
Weight loss	3/39 (7.7%)
Alanine aminotransferase increased	8/39 (20.5%)
Alkaline phosphatase increased	22/39 (56.4%)
Aspartate aminotransferase increased	25/39 (64.1%)
Creatine phosphokinase increased	1/39 (2.6%)
Creatinine increased	5/39 (12.8%)
Protein urine positive	1/39 (2.6%)
Metabolism and nutrition disorders
Obesity	1/39 (2.6%)
Glucose intolerance	3/39 (7.7%)
Anorexia	3/39 (7.7%)
Dehydration	2/39 (5.1%)
Hyperglycemia	23/39 (59%)
Hypoalbuminemia	13/39 (33.3%)
Hypocalcemia	6/39 (15.4%)
Hypercalcemia	3/39 (7.7%)
Hypercholesteremia	6/39 (15.4%)
Hypoglycemia	5/39 (12.8%)
Hypermagnesemia	2/39 (5.1%)
Hypophosphatemia	3/39 (7.7%)
Hypokalemia	10/39 (25.6%)
Hyperkalemia	3/39 (7.7%)
Hyponatremia	12/39 (30.8%)
Hypertriglyceridemia	1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Fibrosis	2/39 (5.1%)
Arthritis	1/39 (2.6%)
Osteoporosis	1/39 (2.6%)
Back pain	14/39 (35.9%)
Bone pain	11/39 (28.2%)
Buttock pain	1/39 (2.6%)
Chest wall pain	1/39 (2.6%)
Joint pain	12/39 (30.8%)
Myalgia	5/39 (12.8%)
Neck pain	3/39 (7.7%)
Pain	11/39 (28.2%)
Pain in extremity	5/39 (12.8%)
Nervous system disorders
Dysgeusia	2/39 (5.1%)
Ataxia	1/39 (2.6%)
Cognitive disturbance	1/39 (2.6%)
Depressed level of consciousness	2/39 (5.1%)
Dizziness	4/39 (10.3%)
Memory impairment	4/39 (10.3%)
Peripheral sensory neuropathy	19/39 (48.7%)
Tremor	1/39 (2.6%)
Trigeminal nerve disorder	1/39 (2.6%)
Headache	7/39 (17.9%)
Psychiatric disorders
Insomnia	2/39 (5.1%)
Agitation	1/39 (2.6%)
Anxiety	11/39 (28.2%)
Confusion	3/39 (7.7%)
Depression	5/39 (12.8%)
Renal and urinary disorders
Ureteric hemorrhage	1/39 (2.6%)
Urethral pain	1/39 (2.6%)
Cystitis	1/39 (2.6%)
Ureteric obstruction	2/39 (5.1%)
Urinary frequency	1/39 (2.6%)
Urinary retention	1/39 (2.6%)
Urine discoloration	1/39 (2.6%)
Urogenital disorder	1/39 (2.6%)
Reproductive system and breast disorders
Breast pain	2/39 (5.1%)
Pelvic pain	2/39 (5.1%)
Irregular menstruation	1/39 (2.6%)
Vaginal dryness	2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	11/39 (28.2%)
Dyspnea	8/39 (20.5%)
Laryngeal edema	1/39 (2.6%)
Pneumonitis	1/39 (2.6%)
Voice alteration	3/39 (7.7%)
Skin and subcutaneous tissue disorders
Sweating	1/39 (2.6%)
Alopecia	2/39 (5.1%)
Hand-and-foot syndrome	2/39 (5.1%)
Nail disorder	2/39 (5.1%)
Pruritus	3/39 (7.7%)
Rash desquamating	9/39 (23.1%)
Skin disorder	5/39 (12.8%)
Skin hyperpigmentation	1/39 (2.6%)
Vascular disorders
Hot flashes	8/39 (20.5%)
Lymphedema	1/39 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.