Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly Paclitaxel and Chemotherapy for HER2 Positive Breast Cancer

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01855828
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The main goal of this clinical trial is to test if adding pertuzumab (Perjeta), improves the anticancer activity of the combination chemotherapy regimen of trastuzumab (Herceptin) concomitant with paclitaxel, 5-fluorouracil, epirubicin, and cyclophosphamide (T-FEC). The study will also test the safety of this therapy.

Condition or Disease	Intervention/Treatment	Phase
Her2-Positive Breast Cancer	Drug: Pertuzumab; Drug: Trastuzumab; Drug: Paclitaxel; Drug: 5-fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide	Phase 2

Detailed Description

Subjects will receive 6 months of T-FEC chemotherapy concomitant with trastuzumab and pertuzumab before surgery. Subsequently, subjects will undergo surgery to remove any cancer from the breast and axillary lymph nodes that may have survived the chemotherapy. It is expected that the majority of women will have no viable cancer left in the breast or lymph nodes by the time all chemotherapy is completed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Arm, Neoadjuvant, Phase II Trial of Pertuzumab and Trastuzumab Administered Concomitantly With Weekly Paclitaxel and FEC for Clinical Stage I-II HER2-Positive Breast Cancer
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chemo plus Pertuzumab,Trastuzumab During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC).

Drug: Pertuzumab; First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total); Other Names: Perjeta ; Drug: Trastuzumab; For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total).; Other Names: Herceptin ; Drug: Paclitaxel; Administered at 80mg/m2 every week from week 1 to 12 (12 doses total).; Other Names: Taxol ; Drug: 5-fluorouracil; Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).; Other Names: 5-FU ; Drug: Epirubicin; Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total).; Other Names: Ellence ; Drug: Cyclophosphamide; Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).; Other Names: Cytoxan

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With a Pathologic Complete Response Rate [20 weeks]

   To estimate the pathologic complete response rate (pCR) when pertuzumab is added to weekly trastuzumab/paclitaxel followed by trastuzumab/5-fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy in HER2-positive breast cancer. This study will assess pCR rates separately in ER+ and ER- cancers. Pathologic complete response is defined as no evidence of viable invasive tumor cells at the primary tumor site and axillary lymph nodes in the surgical specimen. Residual Disease (RD) is defined as: Any invasive cancer in the breast or axillary lymph nodes in the surgical specimen.

Secondary Outcome Measures

1. Cardiac Safety [Up to 1 year post surgery]

   To assess the safety of the regimen, cardiac safety was measured by rates of clinically symptomatic congestive heart failure, asymptomatic decrease in LVEF >10%, and decrease of LVEF below normal level. This was assessed up to 1 year following surgery.

2. Count of Patients With Clinical Response [Up to 28 weeks]

   To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.

3. Residual Cancer Burden Score [Up to 28 weeks]

   To assess cancer burben, the Residual Cancer Burden (RCB) score was used. This score has a range of 0 - III, where III (3) is the worst level of burden.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following NCCN practice guidelines.

HER2 overexpression or amplification will be based on local test results and is defined as either:

(i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10% of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome 17 signals) of greater than or equal to 2.0.

• Patients with synchronous bilateral breast cancers are eligible if at least one of the tumors is HER2-positive.

• Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA, or within the institution's normal limits.

• Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer patients who are sexually active have to agree to practice contraception while participating in the trial and for 3 month after completion of therapy.

• Adequate bone marrow function as indicated by the following:

• ANC greater than or equal to 1500/uL

• Platelets greater than or equal to 100,000/uL

• Hemoglobin greater than or equal to 10 g/dL

• Adequate renal function, as indicated by creatinine less than or equal to 1.5 times upper limit of normal (ULN)

• Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and AST or ALT less than or equal to 2x ULN.

• Signed informed consent.

Exclusion Criteria:

Patients will be excluded from the study based on any of the following criteria:

• Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy, modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed for pathologic response accurately.

• Patients who are high risk for developing the following anthracycline, paclitaxel, trastuzumab or pertuzumab related toxicities including:

History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3 Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients older than age 65 due to increased risk of cardiotoxicity

• Active infection requiring systemic antibiotic therapy.

• Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University Smilow Cancer Hospital	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University
• Genentech, Inc.

Investigators

• Principal Investigator: Lajos Pusztai, MD, Yale University

Study Documents (Full-Text)

• Informed Consent Form - Aug 7, 2017
• Study Protocol and Statistical Analysis Plan - Jun 23, 2016

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01855828
• Other Study ID Numbers: 1305012136
• First Posted: May 17, 2013
• Last Update Posted: Mar 31, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Cyclophosphamide; Fluorouracil; Trastuzumab; Epirubicin; Pertuzumab

Study Results

Participant Flow

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Period Title: Overall Study
STARTED	50
COMPLETED	48
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Overall Participants	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	50 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	36 72%
African American	4 8%
Asian	2 4%
Hispanic	6 12%
Unknown	2 4%
Region of Enrollment (participants) [Number]
United States	50 100%
Hormone receptor status (Count of Participants)
Estrogen Receptor + / Progesterone Receptor +	20 40%
Estrogen Receptor + / Progesterone Receptor -	4 8%
Estrogen Receptor - / Progesterone Receptor -	26 52%
HER2 status (Count of Participants)
Fluorescence in situ hybridization (FISH) positive	27 54%
Immunohistochemistry (IHC) 3+	23 46%
Clinical Tumor Status (Count of Participants)
T1: Tumor is 2 cm or smaller	18 36%
T2: Tumor is larger than 2 cm, but no larger than	25 50%
T3: Tumor is larger than 5 cm	5 10%
T4: Tumor is any size, but has spread	2 4%
Type of surgery (Count of Participants)
Mastectomy	35 70%
Breast conserving surgery	13 26%
No surgery (dropped out of study)	2 4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With a Pathologic Complete Response Rate
Description	To estimate the pathologic complete response rate (pCR) when pertuzumab is added to weekly trastuzumab/paclitaxel followed by trastuzumab/5-fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy in HER2-positive breast cancer. This study will assess pCR rates separately in ER+ and ER- cancers. Pathologic complete response is defined as no evidence of viable invasive tumor cells at the primary tumor site and axillary lymph nodes in the surgical specimen. Residual Disease (RD) is defined as: Any invasive cancer in the breast or axillary lymph nodes in the surgical specimen.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

For ER-negative cancers, the maximum sample size was set to n = 25 and the regimen would be considered of interest if > 20 patients achieve pCR. For ER-positive patients, the maximum sample size for the ER-positive cohort was set to 39 and the regimen would be considered of interest in this subgroup if > 23 patients achieve pCR.

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Measure Participants	48
HR Positive	.26 0.5%
HR Negative	.80 1.6%

2. Secondary Outcome

Title	Cardiac Safety
Description	To assess the safety of the regimen, cardiac safety was measured by rates of clinically symptomatic congestive heart failure, asymptomatic decrease in LVEF >10%, and decrease of LVEF below normal level. This was assessed up to 1 year following surgery.
Time Frame	Up to 1 year post surgery

Outcome Measure Data

Analysis Population Description

All patients are assessed in each arm.

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab-symptomatic Congestive Heart	Chemo Plus Pertuzumab,Trastuzumab-asympomatic Decrease in LVEF	Chemo Plus Pertuzumab,Trastuzumab-LVEF Below Normal Level
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Measure Participants	50	50	50
Count of Participants [Participants]	0 0%	14 NaN	1 NaN

3. Secondary Outcome

Title	Count of Patients With Clinical Response
Description	To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.
Time Frame	Up to 28 weeks

Outcome Measure Data

Analysis Population Description

All patients are assessed by HR-positive or HR-negative status.

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab HR-positive	Chemo Plus Pertuzumab,Trastuzumab HR-negative
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Measure Participants	23	25
Count of Participants [Participants]	6 12%	20 NaN

4. Secondary Outcome

Title	Residual Cancer Burden Score
Description	To assess cancer burben, the Residual Cancer Burden (RCB) score was used. This score has a range of 0 - III, where III (3) is the worst level of burden.
Time Frame	Up to 28 weeks

Outcome Measure Data

Analysis Population Description

Total participants that were analyzed for this score (n=43).

Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Measure Participants	43
RCB = 0	28 56%
RCB = I (1)	5 10%
RCB = II (2)	4 8%
RCB = III (3)	4 8%

Adverse Events

Time Frame	Up to 28 weeks.
Adverse Event Reporting Description	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. This includes the following; AEs not previously observed in the subject that emerge during the protocol, specified AE reporting period. Complications that occur as a result of protocol-mandated interventions (e.g., invasive procedures such as cardiac catheterizations).
Arm/Group Title	Chemo Plus Pertuzumab,Trastuzumab
Arm/Group Description	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
All Cause Mortality
	Chemo Plus Pertuzumab,Trastuzumab
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	Chemo Plus Pertuzumab,Trastuzumab
	Affected / at Risk (%)	# Events
Total	6/50 (12%)
Cardiac disorders
Ventricular tachycardia	1/50 (2%)	1
General disorders
Fever	1/50 (2%)	1
Flu like symptoms	1/50 (2%)	1
Infections and infestations
Catheter related infection	2/50 (4%)	2
Psychiatric disorders
Suicidal ideation	1/50 (2%)	1
Vascular disorders
Thromboembolic event	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Chemo Plus Pertuzumab,Trastuzumab
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Anemia	36/50 (72%)	65
Febrile neutropenia	3/50 (6%)	3
Cardiac disorders
Palpitations	3/50 (6%)	5
Eye disorders
Blurred vision	5/50 (10%)	5
Watering eyes	12/50 (24%)	13
Gastrointestinal disorders
Abdominal pain	10/50 (20%)	12
Constipation	14/50 (28%)	15
Diarrhea	45/50 (90%)	110
Dry mouth	5/50 (10%)	6
Dyspepsia	7/50 (14%)	8
Gastroesophageal reflux disease	10/50 (20%)	12
Mucositis oral	19/50 (38%)	33
Nausea	41/50 (82%)	67
Stomach pain	3/50 (6%)	3
Vomiting	13/50 (26%)	18
General disorders
Edema limbs	8/50 (16%)	10
Fatigue	43/50 (86%)	59
Infusion related reaction	3/50 (6%)	4
Pain	27/50 (54%)	49
Immune system disorders
Allergic reaction	4/50 (8%)	5
Infections and infestations
Nail infection	6/50 (12%)	6
Skin infection	4/50 (8%)	4
Upper respiratory infection	4/50 (8%)	4
Urinary tract infection	6/50 (12%)	6
Investigations
Alanine aminotransferase increased	27/50 (54%)	52
Alkaline phosphatase increased	6/50 (12%)	8
Aspartate aminotransferase increased	16/50 (32%)	20
Neutrophil count decreased	13/50 (26%)	21
Weight loss	4/50 (8%)	4
White blood cell decreased	21/50 (42%)	47
Metabolism and nutrition disorders
Anorexia	5/50 (10%)	7
Hypoalbuminemia	3/50 (6%)	3
Hypocalcemia	8/50 (16%)	13
Hypokalemia	10/50 (20%)	19
Hypomagnesemia	3/50 (6%)	3
Hyponatremia	3/50 (6%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	5/50 (10%)	5
Back pain	6/50 (12%)	9
Bone pain	5/50 (10%)	7
Myalgia	7/50 (14%)	7
Pain in extremity	7/50 (14%)	7
Nervous system disorders
Dizziness	10/50 (20%)	12
Dysgeusia	10/50 (20%)	11
Headache	16/50 (32%)	20
Paresthesia	4/50 (8%)	5
Peripheral motor neuropathy	7/50 (14%)	8
Peripheral sensory neuropathy	25/50 (50%)	34
Psychiatric disorders
Anxiety	8/50 (16%)	10
Insomnia	18/50 (36%)	21
Renal and urinary disorders
Urinary frequency	3/50 (6%)	3
Urinary tract pain	4/50 (8%)	6
Reproductive system and breast disorders
Breast pain	5/50 (10%)	6
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	19/50 (38%)	22
Cough	9/50 (18%)	10
Dyspnea	10/50 (20%)	10
Epistaxis	35/50 (70%)	40
Nasal congestion	8/50 (16%)	10
Sore throat	6/50 (12%)	6
Skin and subcutaneous tissue disorders
Alopecia	38/50 (76%)	50
Dry skin	8/50 (16%)	8
Nail discoloration	18/50 (36%)	20
Pruritus	7/50 (14%)	8
Rash acneiform	19/50 (38%)	24
Rash maculo-papular	21/50 (42%)	24
Scalp pain	3/50 (6%)	3
Skin hyperpigmentation	4/50 (8%)	5
Vascular disorders
Flushing	3/50 (6%)	3
Hot flashes	20/50 (40%)	22
Hypertension	7/50 (14%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.