Nab-Paclitaxel in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer
Study Details
Study Description
Brief Summary
This phase II trial studies the side effects of nab-paclitaxel in treating older patients with breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- To evaluate the tolerability (grade 2-5 toxicity, neuropathy grade 2 or higher, need for dose reductions, or delays) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer.
SECONDARY OBJECTIVES:
-
To evaluate the efficacy (response and time to progression) of weekly nab-paclitaxel in older adults with locally advanced or metastatic breast cancer using a stratification factor based on patient age (at least 5 patients age 75 years or older and no more than 15 patients age 65-70 years).
-
To explore predictors of the need for dose reduction, dose delays, or grade 2-5 toxicity and neuropathy grade 2 or higher based on a cancer-specific geriatric assessment.
OUTLINE:
Patients receive nab-paclitaxel intravenously (IV) over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (nab-paclitaxel) Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Nab-paclitaxel
Given IV
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 [During and after treatment, up to 2.5 years]
Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to treatment.
- Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment [On treatment, 28 days per cycle up to 30 months]
Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to treatment.
- Rate of Participants With a Dose Reduction [On treatment, up to 30 months]
Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.
- Rate of Participants Requiring Dose Holds [While on treatment, up to 30 months]
Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.
Secondary Outcome Measures
- Response Determined by Response Evaluation Criteria in Solid Tumors [Up to 2.5 years]
Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for objective response rate (complete response [CR] + partial response [PR]). RECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Additionally, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
- Median Progression Free Survival (PFS) [From the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed for about 1.5 years]
PFS will be estimated using the product limit method of Kaplan and Meier.
- Cancer-specific Geriatric (CARG) Assessment [CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months]
General linear models and descriptive methods will be used to explore factors as identified by a CARG assessment that may be predictive of toxicity (grade 3 or higher adverse events) or dose reduction. The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxicity. Scores from 0 to 5 are considered low risk, 6 to 9 are considered intermediate risk, and 10 to 19 are considered high risk.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Locally advanced or metastatic breast cancer
-
Any estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2neu) status as long as the patient will receive nab-paclitaxel alone
-
First or second line chemotherapy treatment for metastatic disease
-
Karnofsky performance status (KPS) >= 70%
-
Resolution of grade >= 2 toxicity from prior therapy (other than alopecia)
-
Peripheral neuropathy =< grade 1
-
Absolute neutrophil count >= 1,500/mm^3
-
Platelets >= 100,000 cells/mm^3
-
Hemoglobin (Hb) >= 9.0 g/dl
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
-
Alkaline phosphatase =< 2.5 x upper limit of normal unless bone metastasis are present in the absence of liver metastases
-
Bilirubin =< 1.5 mg/dl
-
Creatinine clearance (calculated or 24 hour) >= 30 ml/min
-
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
-
Patients may not be receiving any other investigational agents
-
Untreated central nervous system (CNS) metastases or symptomatic CNS metastases requiring escalating doses of corticosteroids
-
Known history of allergic reactions to paclitaxel
-
Presence of any serious or uncontrolled infection
-
Receipt of a taxane for adjuvant therapy or metastatic disease in the last 12 months
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | City of Hope medical | Duarte | California | United States | 91010 |
2 | City of Hope Antelope Valley | Lancaster | California | United States | 93534 |
3 | City of Hope South Pasadena | South Pasadena | California | United States | 91030 |
4 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- City of Hope Medical Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Mina Sedrak, City of Hope Medical Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- 11139
- NCI-2011-03295
- 118196
- 124494
- 11139
- P30CA033572
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Period Title: Overall Study | |
STARTED | 40 |
COMPLETED | 40 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Overall Participants | 40 |
Age (years) [Mean (Full Range) ] | |
Mean (Full Range) [years] |
73
|
Sex: Female, Male (Count of Participants) | |
Female |
38
95%
|
Male |
2
5%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
7
17.5%
|
Not Hispanic or Latino |
33
82.5%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
6
15%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
4
10%
|
White |
29
72.5%
|
More than one race |
1
2.5%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
40
100%
|
Receptor status (Count of Participants) | |
HR-positive |
30
75%
|
Triple-negative |
10
25%
|
Outcome Measures
Title | Percent of Participants With Grade 2-5 Toxicity Using National Cancer Institute Common Toxicity Criteria Version 4.0 |
---|---|
Description | Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to treatment. |
Time Frame | During and after treatment, up to 2.5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Number (95% Confidence Interval) [percentage of participants] |
90
225%
|
Title | Percent of Participants With Grade 3 or Higher Toxicities Attributable to Treatment |
---|---|
Description | Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to treatment. |
Time Frame | On treatment, 28 days per cycle up to 30 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Number (95% Confidence Interval) [percentage of participants] |
58
145%
|
Title | Rate of Participants With a Dose Reduction |
---|---|
Description | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. |
Time Frame | On treatment, up to 30 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Number (95% Confidence Interval) [percentage of participants] |
50
125%
|
Title | Rate of Participants Requiring Dose Holds |
---|---|
Description | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction. |
Time Frame | While on treatment, up to 30 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Number (95% Confidence Interval) [percentage of participants] |
75
187.5%
|
Title | Response Determined by Response Evaluation Criteria in Solid Tumors |
---|---|
Description | Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for objective response rate (complete response [CR] + partial response [PR]). RECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Additionally, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study |
Time Frame | Up to 2.5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Complete remission |
1
2.5%
|
Partial remission |
13
32.5%
|
Stable disease |
16
40%
|
Progressive disease |
4
10%
|
Off treatment prior to disease assessment |
6
15%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment (Nab-paclitaxel) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Percent |
Estimated Value | 35 | |
Confidence Interval |
(2-Sided) 95% 21 to 52 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | 35% of participants were responders (CR+PR). |
Title | Median Progression Free Survival (PFS) |
---|---|
Description | PFS will be estimated using the product limit method of Kaplan and Meier. |
Time Frame | From the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed for about 1.5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Median (95% Confidence Interval) [months] |
6.5
|
Title | Cancer-specific Geriatric (CARG) Assessment |
---|---|
Description | General linear models and descriptive methods will be used to explore factors as identified by a CARG assessment that may be predictive of toxicity (grade 3 or higher adverse events) or dose reduction. The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxicity. Scores from 0 to 5 are considered low risk, 6 to 9 are considered intermediate risk, and 10 to 19 are considered high risk. |
Time Frame | CARG measured prior to treatment, toxicities and dose reduction measured up to 30 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Nab-paclitaxel) |
---|---|
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies |
Measure Participants | 40 |
Low CARG chemotherapy toxicity risk |
21
52.5%
|
Intermediate CARG chemotherapy toxicity risk |
15
37.5%
|
High CARG chemotherapy toxicity risk |
4
10%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment (Nab-paclitaxel) |
---|---|---|
Comments | CARG chemotherapy toxicity risk predictive of chemotherapy toxicity (grade 3) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.01 |
Comments | ||
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 5.8 | |
Confidence Interval |
(2-Sided) 95% 1.3 to 33.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio is intermediate/high toxicity risk over low toxicity risk |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Treatment (Nab-paclitaxel) |
---|---|---|
Comments | CARG chemotherapy toxicity risk predictive of dose reduction due to chemotherapy toxicity | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.02 |
Comments | ||
Method | t-test, 2 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of group means |
Estimated Value | 1.38 | |
Confidence Interval |
(2-Sided) 95% 1.04 to 1.80 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio is dose reduction over no dose reduction. |
Adverse Events
Time Frame | On study, up to 2.5 years | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Treatment (Nab-paclitaxel) | |
Arm/Group Description | Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Nab-paclitaxel: Given IV Questionnaire Administration: Ancillary studies | |
All Cause Mortality |
||
Treatment (Nab-paclitaxel) | ||
Affected / at Risk (%) | # Events | |
Total | 35/40 (87.5%) | |
Serious Adverse Events |
||
Treatment (Nab-paclitaxel) | ||
Affected / at Risk (%) | # Events | |
Total | 14/40 (35%) | |
Blood and lymphatic system disorders | ||
Anemia | 1/40 (2.5%) | |
Cardiac disorders | ||
Atrial fibrillation | 1/40 (2.5%) | |
Cardiac disorders - Other, specify | 1/40 (2.5%) | |
Heart failure | 1/40 (2.5%) | |
Supraventricular tachycardia | 1/40 (2.5%) | |
Gastrointestinal disorders | ||
Abdominal pain | 1/40 (2.5%) | |
Constipation | 1/40 (2.5%) | |
Diarrhea | 2/40 (5%) | |
Mucositis oral | 1/40 (2.5%) | |
Nausea | 4/40 (10%) | |
Vomiting | 4/40 (10%) | |
General disorders | ||
Fatigue | 1/40 (2.5%) | |
Non-cardiac chest pain | 1/40 (2.5%) | |
Immune system disorders | ||
Allergic reaction | 1/40 (2.5%) | |
Infections and infestations | ||
Urinary tract infection | 1/40 (2.5%) | |
Bronchial infection | 1/40 (2.5%) | |
Investigations | ||
Activated partial thromboplastin time prolonged | 1/40 (2.5%) | |
Metabolism and nutrition disorders | ||
Dehydration | 2/40 (5%) | |
Hyponatermia | 1/40 (2.5%) | |
Musculoskeletal and connective tissue disorders | ||
Muscle weakness upper limb | 1/40 (2.5%) | |
Nervous system disorders | ||
Headache | 1/40 (2.5%) | |
Stroke | 1/40 (2.5%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 1/40 (2.5%) | |
Dyspnea | 2/40 (5%) | |
Hypoxia | 1/40 (2.5%) | |
Respiratory failure | 1/40 (2.5%) | |
Vascular disorders | ||
Hematoma | 1/40 (2.5%) | |
Other (Not Including Serious) Adverse Events |
||
Treatment (Nab-paclitaxel) | ||
Affected / at Risk (%) | # Events | |
Total | 40/40 (100%) | |
Blood and lymphatic system disorders | ||
Anemia | 19/40 (47.5%) | |
Eye disorders | ||
Conjunctivitis | 2/40 (5%) | |
Gastrointestinal disorders | ||
Diarrhea | 4/40 (10%) | |
General disorders | ||
Edema limbs | 2/40 (5%) | |
Pain | 3/40 (7.5%) | |
Fatigue | 23/40 (57.5%) | |
Immune system disorders | ||
Allergic reaction | 2/40 (5%) | |
Infections and infestations | ||
Nail infection | 2/40 (5%) | |
Infections and infestations - Other, specify | 3/40 (7.5%) | |
Urinary tract infection | 4/40 (10%) | |
Skin infection | 6/40 (15%) | |
Upper respiratory infection | 7/40 (17.5%) | |
Investigations | ||
Aspartate aminotransferase increased | 2/40 (5%) | |
Weight gain | 2/40 (5%) | |
Lymphocyte count decreased | 8/40 (20%) | |
Neutrophil count decreased | 17/40 (42.5%) | |
White blood cell decreased | 25/40 (62.5%) | |
Metabolism and nutrition disorders | ||
Hyperglycemia | 3/40 (7.5%) | |
Hypokalemia | 4/40 (10%) | |
Dehydration | 5/40 (12.5%) | |
Hypocalcemia | 6/40 (15%) | |
Musculoskeletal and connective tissue disorders | ||
Pain in extremity | 2/40 (5%) | |
Nervous system disorders | ||
Peripheral sensory neuropathy | 6/40 (15%) | |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnea | 3/40 (7.5%) | |
Vascular disorders | ||
Thromboembolic event | 2/40 (5%) | |
Hypotension | 3/40 (7.5%) | |
Hypertension | 18/40 (45%) |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Dr. Mina Sedrak |
---|---|
Organization | City of Hope |
Phone | 626-359-8111 |
msedrak@coh.org |
- 11139
- NCI-2011-03295
- 118196
- 124494
- 11139
- P30CA033572