Nab-Paclitaxel in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01463072
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 40
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 125.9
• Patients Per Site: 10
• Patients Per Site Per Month: 0.1

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
Locally Advanced Breast Carcinoma; Metastatic Breast Carcinoma; Recurrent Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7	Other: Laboratory Biomarker Analysis; Drug: Nab-paclitaxel; Other: Questionnaire Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. 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:

1. 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).

2. 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

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Tolerability of Nanoparticle Albumin Bound Paclitaxel (Abraxane) in Patients 65 and Older With Locally Advanced or Metastatic Breast Cancer
• Actual Study Start Date: Jun 19, 2012
• Actual Primary Completion Date: May 17, 2017
• Anticipated Study Completion Date: Dec 15, 2022

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: ABI 007 ABI-007 Abraxane Albumin-bound Paclitaxel Albumin-Stabilized Nanoparticle Paclitaxel Nanoparticle Albumin-bound Paclitaxel Nanoparticle Paclitaxel Paclitaxel Albumin paclitaxel albumin-stabilized nanoparticle formulation protein-bound paclitaxel ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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

1. 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

2. 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.

3. 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

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

• Study Protocol and Statistical Analysis Plan - Sep 23, 2019

More Information

Additional Information:

• Link to the study

Publications

• Hurria A, Soto-Perez-de-Celis E, Blanchard S, Burhenn P, Yeon CH, Yuan Y, Li D, Katheria V, Waisman JR, Luu TH, Somlo G, Noonan AM, Lee T, Sudan N, Chung S, Rotter A, Arsenyan A, Levi A, Choi J, Rubalcava A, Morrison R, Mortimer JE. A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology. Clin Breast Cancer. 2019 Apr;19(2):89-96. doi: 10.1016/j.clbc.2018.10.002. Epub 2018 Oct 16.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT01463072
• Other Study ID Numbers: 11139; NCI-2011-03295; 118196; 124494; 11139; P30CA033572
• First Posted: Nov 1, 2011
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

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

1. Primary Outcome

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%

2. Primary Outcome

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%

3. Primary Outcome

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%

4. Primary Outcome

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%

5. Secondary Outcome

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).

6. Secondary Outcome

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

7. Secondary Outcome

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
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

[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.