Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT01401959
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 127
• Locations: 18
• Arms: 3
• Actual Duration (Months): 66.3
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The investigators propose to evaluate eribulin as adjuvant therapy in breast cancer patients who have residual invasive disease in breast or lymph node tissue following standard neoadjuvant chemotherapy and surgery regimen. Three cohorts of patients will be evaluated separately based on tumor type: triple-negative, hormone-receptor-positive/HER2-negative, and HER2-positive breast cancers.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Eribulin; Drug: Trastuzumab	Phase 2

Detailed Description

This is a non-randomized, open-label trial to evaluate 6 cycles of eribulin in female patients with invasive breast cancer who do not achieve pathologic complete response (pCR) after treatment with a standard neoadjuvant chemotherapy and surgery regimen. Patients will be randomized into three cohorts according to tumor-type: triple-negative (Cohort A), hormone-receptor-positive/HER2-negative (Cohort B), and HER2-positive (Cohort C) tumors. Patients will receive eribulin for 6 cycles (1 cycle = 21 days). Patients with HER2-positive tumors will also receive trastuzumab. Patients in all cohorts will be allowed to receive locoregional radiotherapy and/or adjuvant hormonal therapy per institutional guidelines.

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
• Actual Study Start Date: Sep 23, 2011
• Actual Primary Completion Date: Apr 3, 2017
• Actual Study Completion Date: Apr 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Triple-negative breast cancer Eribulin 1.4 mg/m^2 intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Names: Halaven
Experimental: Cohort B: ER/PR+ /HER2- breast cancer Eribulin 1.4 mg/m^2 intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Names: Halaven
Experimental: Cohort C: HER2+ breast cancer Eribulin 1.4 mg/m^2 intravenously (IV) Trastuzumab 6mg/kg intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Names: Halaven ; Drug: Trastuzumab; 6 mg/kg IV Day 1 every 21 days; Other Names: Herceptin

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy [Up to 2 years]

   The percentage of patients that are without evidence of disease recurrence at the 2 year timepoint, as measured from date of first protocol treatment date to first documented disease progression date or date of death from any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility [up to 18 weeks]

   Examines the feasibility of administering 6 cycles (21 days per cycle) of eribulin without toxicity or disease worsening following standard neoadjuvant chemotherapy and surgery.

2. The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety [Weekly during each 21 day cycle and for 30 days after completion of protocol-specific treatment. After that patients were followed every 3 months for up to 2 years.]

   A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female patients >=18 years-of-age.

2. Histologically confirmed breast cancer prior to surgery with the following staging criteria: T1-T3, T4a, T4b, N0-N2, N3a and M0 (T1N0M0 patients are excluded). Inflammatory disease is excluded.

3. Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or taxane containing chemotherapy (+trastuzumab in HER2-positive patients).

4. Patients must be ≥ 21 days and ≤ 84 days from breast surgery and fully recovered. Patients may have had mastectomy or breast conservation surgery with axillary node dissection.

5. Pathologic CR (pCR) not achieved following neoadjuvant treatment (i.e., residual invasive breast cancer (>5 mm) in the breast or presence of nodal disease at surgery [ypT0/T1a, N1-N3a, M0 or ypT1b-T4, N0-N3a, M0].

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

7. Recovery from any toxic effects of prior therapy to <=Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) except fatigue or alopecia.

8. Peripheral neuropathy Grade <=2 per NCI CTCAE v4.0 at trial entry.

9. Normal left ventricular ejection fraction (LVEF), within the institutional limits of normal, as measured by echocardiography (ECHO) or multi-gated (MUGA) scan in patients to receive trastuzumab with eribulin (HER2-positive).

10. Adequate hematologic, hepatic, and renal function

11. Complete staging work-up to confirm localized disease should include computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan. (Note: a PET/CT is acceptable for baseline imaging in lieu of CT examinations or bone scan). Negative scans performed prior to the initiation of neoadjuvant therapy, or at any subsequent time, are acceptable and do not need to be repeated.

12. Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test performed within 7 days prior to start of trial treatment.

13. Willingness and ability to comply with trial and follow-up procedures.

14. Ability to understand the investigative nature of this trial and give written informed consent.

15. Agree to delay in reconstruction in terms of implants placed in setting of expanders until chemotherapy is completed and the patient has recovered. Expansion of expanders may continue during trial treatment.

Exclusion Criteria:

1. Presence of other active cancers, or history of treatment for invasive cancer <3 years prior to trial entry (except thyroid, cervical cancer). Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

2. Radiotherapy prior to the start of study treatment.

3. History or clinical evidence of central nervous system metastases or other metastatic disease.

4. Non-healed surgical wound.

5. Known or suspected allergy/hypersensitivity to eribulin.

6. Cardiac disease, including: congestive heart failure Class II-IV per New York Heart Association classification;cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months.

7. Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of these drugs 7 days prior to the start of study treatment.

8. Women who are pregnant or lactating. All females of child-bearing potential must have negative serum pregnancy test within 48 hours prior to trial treatment.

9. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.

10. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs (using Bazett's formula).

11. Minor surgical procedures (with the exception of the placement of port-a-cath or other central venous access) performed less than 7 days prior to beginning protocol treatment.

12. History of cerebrovascular accident including transient ischemic attack (TIA), or untreated deep venous thrombosis (DVT)/ pulmonary embolism (PE) within the past 6 months. Note: Patients with recent DVT/PE receiving treatment with a stable dose of therapeutic anti-coagulating agents are eligible.

13. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.

14. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the trial participation or investigational product(s) administration or may interfere with the interpretation of the results.

15. Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists North	Fort Myers	Florida	United States	33916
2	Florida Cancer Specialists South	Fort Myers	Florida	United States	33916
3	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida	United States	33805
4	Florida Hospital Cancer Insitute	Orlando	Florida	United States	32804
5	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
6	Providence Medical Group	Terre Haute	Indiana	United States	47802
7	Mercy Hospital	Portland	Maine	United States	04101
8	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
9	National Capital Clinical Research Consortium	Bethesda	Maryland	United States	20817
10	Nebraska Methodist Cancer Center	Omaha	Nebraska	United States	68114
11	Atlantic Health System	Morristown	New Jersey	United States	07960
12	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey	United States	07960
13	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
14	South Carolina Oncology Associates	Columbia	South Carolina	United States	29210
15	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
16	Tennessee Oncology	Nashville	Tennessee	United States	37203
17	Texas Health Physician Group	Arlington	Texas	United States	76011
18	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Eisai Inc.

Investigators

• Study Chair: Denise A Yardley, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

• Study Protocol - Mar 20, 2013
• Statistical Analysis Plan - Apr 3, 2018

More Information

Publications

• Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2.
• Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1275-81. doi: 10.1200/JCO.2007.14.4147. Epub 2008 Feb 4.
• Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001 Feb 1;61(3):1013-21.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT01401959
• Other Study ID Numbers: SCRI BRE 186
• First Posted: Jul 26, 2011
• Last Update Posted: Jun 15, 2018
• Last Verified: May 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by SCRI Development Innovations, LLC: Metastatic Breast Cancer; Adjuvant; Residual Disease; eribulin; Trastuzumab
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab

Study Results

Participant Flow

Recruitment Details	Between September 2011 to April 2015, 127 female patients who did not achieve a pathologic complete response (pCR i.e. have residual invasive disease in breast or lymph node tissue) after treatment with a standard neoadjuvant chemotherapy regimen and surgery were enrolled. Of those 127 patients enrolled, 126 patients received treatment.

Arm/Group Title	Cohort A: Triple-negative Breast Cancer Patients	Cohort B: ER/PR Positive/HER2-negative Breast Cancer	Cohort C: HER2-positive Breast Cancer Patients
Arm/Group Description	Patients with Triple-Negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with ER positive and/or PR positive, HER-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.
Period Title: Enrolled
STARTED	54	42	31
COMPLETED	53	42	31
NOT COMPLETED	1	0	0
Period Title: Enrolled
STARTED	53	42	31
COMPLETED	46	34	26
NOT COMPLETED	7	8	5

Baseline Characteristics

Arm/Group Title	Cohort A: Triple-negative Breast Cancer Patients	Cohort B: ER/PR Positive/HER2-negative Breast Cancer Patients	Cohort C: HER2-positive Breast Cancer Patients	Total
Arm/Group Description	Patients with triple-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with hormone receptor positive (ER and/or PR positive), HER negative breast cancer breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.	Total of all reporting groups
Overall Participants	53	42	31	126
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49	55	52	52
Sex: Female, Male (Count of Participants)
Female	53 100%	42 100%	31 100%	126 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 22.6%	4 9.5%	2 6.5%	18 14.3%
White	39 73.6%	37 88.1%	28 90.3%	104 82.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 3.8%	1 2.4%	1 3.2%	4 3.2%
Region of Enrollment (Count of Participants)
United States	53 100%	42 100%	31 100%	126 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy
Description	The percentage of patients that are without evidence of disease recurrence at the 2 year timepoint, as measured from date of first protocol treatment date to first documented disease progression date or date of death from any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Patients who receive at least one dose of treatment

Arm/Group Title	Cohort A: Triple-negative Breast Cancer Patients	Cohort B: ER/PR Positive/HER2-negative Breast Cancer Patients	Cohort C: HER2-positive Breast Cancer Patients
Arm/Group Description	Patients with triple-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with hormone receptor positive (ER and/or PR positive), HER negative breast cancer breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.
Measure Participants	53	42	31
Number (95% Confidence Interval) [percentage of patients]	56	83	73

2. Secondary Outcome

Title	Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility
Description	Examines the feasibility of administering 6 cycles (21 days per cycle) of eribulin without toxicity or disease worsening following standard neoadjuvant chemotherapy and surgery.
Time Frame	up to 18 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of treatment

Arm/Group Title	Cohort A: Triple-negative Breast Cancer Patients	Cohort B: ER/PR Positive/HER2-negative Breast Cancer	Cohort C: HER2-positive Breast Cancer Patients
Arm/Group Description	Patients with Triple-Negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with ER positive and/or PR positive, HER-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.
Measure Participants	53	42	31
Count of Participants [Participants]	46 86.8%	34 81%	26 83.9%

3. Secondary Outcome

Title	The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety
Description	A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.
Time Frame	Weekly during each 21 day cycle and for 30 days after completion of protocol-specific treatment. After that patients were followed every 3 months for up to 2 years.

Outcome Measure Data

Analysis Population Description

All patients who receive at least one dose of treatment.

Arm/Group Title	Cohort A: Triple-negative Breast Cancer Patients	Cohort B: ER/PR Positive/HER2-negative Breast Cancer	Cohort C: HER2-positive Breast Cancer Patients
Arm/Group Description	Patients with Triple-Negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with ER positive and/or PR positive, HER-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.	Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.
Measure Participants	53	42	31
Count of Participants [Participants]	50 94.3%	41 97.6%	31 100%

Adverse Events

Time Frame	Day 1 and Day 8 of every treatment cycle and 30 days after discontinuation or completion of treatment for up to 22.2 weeks
Adverse Event Reporting Description	All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Arm/Group Title	Cohort A: Triple-negative Breast Cancer		Cohort B: ER/PR Positive/HER2-negative Breast Cancer		Cohort C: HER2 Positive Breast Cancer
Arm/Group Description	Patients with Triple-Negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.		Patients with ER positive and/or PR positive, HER-negative breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route.		Patients with HER2-postive breast cancer who do not have a pathological complete response following neoadjuvant therapy and surgery will receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days for 6 cycles via the intravenous (IV) route. Patients will also concurrently receive trastuzumab 6 mg/kg IV on Day 1 every 21 days.
All Cause Mortality
	Cohort A: Triple-negative Breast Cancer		Cohort B: ER/PR Positive/HER2-negative Breast Cancer		Cohort C: HER2 Positive Breast Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/53 (11.3%)		4/42 (9.5%)		1/31 (3.2%)
Serious Adverse Events
	Cohort A: Triple-negative Breast Cancer		Cohort B: ER/PR Positive/HER2-negative Breast Cancer		Cohort C: HER2 Positive Breast Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/53 (15.1%)		1/42 (2.4%)		3/31 (9.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Cardiac disorders
Cardiac failure congestive	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Ventricular arrhythmia	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Infections and infestations
Cellulitis	0/53 (0%)		0/42 (0%)		1/31 (3.2%)
Mastitis	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Pneumonia	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Sinusitis	0/53 (0%)		0/42 (0%)		1/31 (3.2%)
Tracheobronchitis	0/53 (0%)		1/42 (2.4%)		0/31 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/53 (0%)		0/42 (0%)		1/31 (3.2%)
Hyperglycaemia	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Nervous system disorders
Seizure	1/53 (1.9%)		0/42 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Cohort A: Triple-negative Breast Cancer		Cohort B: ER/PR Positive/HER2-negative Breast Cancer		Cohort C: HER2 Positive Breast Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/52 (100%)		42/42 (100%)		31/31 (100%)
Blood and lymphatic system disorders
Anemia	20/52 (38.5%)		13/42 (31%)		16/31 (51.6%)
Ear and labyrinth disorders
Tinnitus	2/52 (3.8%)		0/42 (0%)		2/31 (6.5%)
Eye disorders
Blurred Vision	2/52 (3.8%)		2/42 (4.8%)		2/31 (6.5%)
Watering Eyes	5/52 (9.6%)		5/42 (11.9%)		1/31 (3.2%)
Gastrointestinal disorders
Nausea	18/52 (34.6%)		16/42 (38.1%)		14/31 (45.2%)
Constipation	14/52 (26.9%)		13/42 (31%)		9/31 (29%)
Diarrhea	8/52 (15.4%)		10/42 (23.8%)		6/31 (19.4%)
Vomiting	6/52 (11.5%)		2/42 (4.8%)		5/31 (16.1%)
Abdominal Pain	5/52 (9.6%)		2/42 (4.8%)		5/31 (16.1%)
Mucositis	4/52 (7.7%)		6/42 (14.3%)		4/31 (12.9%)
Dyspepsia	8/52 (15.4%)		7/42 (16.7%)		3/31 (9.7%)
Gastroesophageal Reflux Disease	3/52 (5.8%)		4/42 (9.5%)		3/31 (9.7%)
Cheilitis	0/52 (0%)		0/42 (0%)		2/31 (6.5%)
Dry Mouth	3/52 (5.8%)		2/42 (4.8%)		0/31 (0%)
General disorders
Fatigue	33/52 (63.5%)		26/42 (61.9%)		23/31 (74.2%)
Edema	4/52 (7.7%)		7/42 (16.7%)		6/31 (19.4%)
Fever	1/52 (1.9%)		5/42 (11.9%)		3/31 (9.7%)
Pain	7/52 (13.5%)		4/42 (9.5%)		2/31 (6.5%)
Non-Cardiac Chest Pain	1/52 (1.9%)		1/42 (2.4%)		2/31 (6.5%)
Chills	2/52 (3.8%)		5/42 (11.9%)		1/31 (3.2%)
Infections and infestations
Upper Respiratory Infection	7/52 (13.5%)		4/42 (9.5%)		2/31 (6.5%)
Urinary Tract Infection	1/52 (1.9%)		0/42 (0%)		2/31 (6.5%)
Nail Infection	0/52 (0%)		3/42 (7.1%)		1/31 (3.2%)
Infections And Infestations - Other, Herpes Zoster	3/52 (5.8%)		1/42 (2.4%)		1/31 (3.2%)
Investigations
Neutrophil Count Decreased	26/52 (50%)		21/42 (50%)		17/31 (54.8%)
Leukopenia	15/52 (28.8%)		23/42 (54.8%)		12/31 (38.7%)
Lymphocyte Count Decreased	0/52 (0%)		1/42 (2.4%)		5/31 (16.1%)
Alanine Aminotransferase Increased	3/52 (5.8%)		6/42 (14.3%)		3/31 (9.7%)
Platelet Count Decreased	3/52 (5.8%)		4/42 (9.5%)		2/31 (6.5%)
Aspartate Aminotransferase Increased	3/52 (5.8%)		5/42 (11.9%)		0/31 (0%)
Metabolism and nutrition disorders
Anorexia	3/52 (5.8%)		5/42 (11.9%)		3/31 (9.7%)
Hypomagnesemia	3/52 (5.8%)		3/42 (7.1%)		3/31 (9.7%)
Hyperglycemia	5/52 (9.6%)		4/42 (9.5%)		2/31 (6.5%)
Dehydration	2/52 (3.8%)		1/42 (2.4%)		2/31 (6.5%)
Hyponatremia	0/52 (0%)		3/42 (7.1%)		1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/52 (38.5%)		8/42 (19%)		12/31 (38.7%)
Myalgia	13/52 (25%)		9/42 (21.4%)		9/31 (29%)
Bone Pain	7/52 (13.5%)		7/42 (16.7%)		4/31 (12.9%)
Pain In Extremity	7/52 (13.5%)		4/42 (9.5%)		3/31 (9.7%)
Generalized Muscle Weakness	0/52 (0%)		0/42 (0%)		3/31 (9.7%)
Back Pain	4/52 (7.7%)		3/42 (7.1%)		2/31 (6.5%)
Nervous system disorders
Peripheral Sensory Neuropathy	24/52 (46.2%)		25/42 (59.5%)		16/31 (51.6%)
Headache	11/52 (21.2%)		12/42 (28.6%)		5/31 (16.1%)
Dizziness	9/52 (17.3%)		6/42 (14.3%)		3/31 (9.7%)
Dysgeusia	7/52 (13.5%)		2/42 (4.8%)		1/31 (3.2%)
Paresthesia	4/52 (7.7%)		1/42 (2.4%)		1/31 (3.2%)
Psychiatric disorders
Insomnia	11/52 (21.2%)		8/42 (19%)		5/31 (16.1%)
Anxiety	5/52 (9.6%)		7/42 (16.7%)		5/31 (16.1%)
Depression	4/52 (7.7%)		5/42 (11.9%)		4/31 (12.9%)
Cognitive Disturbance	0/52 (0%)		0/42 (0%)		2/31 (6.5%)
Reproductive system and breast disorders
Breast Pain	4/52 (7.7%)		4/42 (9.5%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/52 (9.6%)		6/42 (14.3%)		5/31 (16.1%)
Cough	8/52 (15.4%)		6/42 (14.3%)		3/31 (9.7%)
Nasal Congestion	1/52 (1.9%)		3/42 (7.1%)		3/31 (9.7%)
Allergic Rhinitis	0/52 (0%)		1/42 (2.4%)		3/31 (9.7%)
Sore Throat	4/52 (7.7%)		4/42 (9.5%)		2/31 (6.5%)
Respiratory, Thoracic And Mediastinal Disorders - Other, Runny Nose	3/52 (5.8%)		4/42 (9.5%)		1/31 (3.2%)
Skin and subcutaneous tissue disorders
Alopecia	11/52 (21.2%)		11/42 (26.2%)		5/31 (16.1%)
Rash	6/52 (11.5%)		5/42 (11.9%)		5/31 (16.1%)
Skin And Subcutaneous Tissue Disorders - Other, Erythema	2/52 (3.8%)		2/42 (4.8%)		2/31 (6.5%)
Vascular disorders
Lymphedema	5/52 (9.6%)		1/42 (2.4%)		4/31 (12.9%)
Hot Flashes	5/52 (9.6%)		4/42 (9.5%)		3/31 (9.7%)
Hypertension	3/52 (5.8%)		6/42 (14.3%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.