Carboplatin, Abraxane, Avastin as Neoadjuvant Therapy for Her2-Negative Breast Cancer

• Sponsor: William Sikov MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00723125
• Collaborator: Yale University (Other)
• Enrollment: 60
• Locations: 5
• Arms: 2
• Duration (Months): 68.4
• Patients Per Site: 12
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

In the MDACC/BrUOG neoadjuvant trial with weekly paclitaxel followed by Fluorouracil Plus Doxorubicin and Cyclophosphamide (FAC), the pathologic complete response (pCR) rate in HER2(-) patients was 20%. The investigators' goal is to develop an induction chemotherapy regimen that will have a pCR rate above 30% in patients with HER2(-) disease. Based on a 1-sided 95% confidence interval using normal approximation with an expected pCR rate of at least 35%, approximately 28 patients are required for each cohort. With an assumed pCR rate of at least 35%, the investigators will have approximately 70% statistical power to conclude, with 90% certainty, that the pCR rate with the novel regimen exceeds 20%. The study will accrue approximately 60 patients in two cohorts with an inevaluable rate that does not exceed 10%.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Abraxane; Drug: Carboplatin; Drug: Avastin	Phase 2

Detailed Description

See above brief summary

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Q3week Carboplatin With Weekly Abraxaneä And Avastin + Subsequent Dose-Dense Ac With Avastin As Neoadjuvant Therapy In Resectable And Unresectable (Stage Iia-Iiib) Her2-Negative Breast Cancer
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: May 15, 2014
• Actual Study Completion Date: May 15, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks	Drug: Abraxane; Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks; Other Names: Paclitaxel Protein-Bound ; Drug: Carboplatin; Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10; Other Names: Paraplatin ; Drug: Avastin; Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10); Other Names: Bevacizumab
Experimental: Cohort 2 Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7 Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks	Drug: Abraxane; Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks; Other Names: Paclitaxel Protein-Bound ; Drug: Carboplatin; Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10; Other Names: Paraplatin ; Drug: Avastin; Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10); Other Names: Bevacizumab

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response Rates at Surgery [at surgery approximately 5 months after initial treatment]

Secondary Outcome Measures

1. Number of Participants With Adverse Events [2 years]

   Measure of safety and tolerability according to CTCAE version 3.0

Eligibility Criteria

Criteria

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

Eligibility criteria

Inclusion criteria:

• Histologically documented adenocarcinoma of the breast

• ANC > 1000 cells

• Female; age > 18

• Zubrod PS 0-1

• Platelets > 100,000

• Stage IIA-IIIB disease

• Total bilirubin < 1.5 ULN

• No evidence of any metastatic disease

• Serum Creatinine < 1.5 gm/dl

• No prior systemic therapy for breast cancer or Creat Cl > 30 ml/min

• Not pregnant or lactating

• Serum ALT < 2.0 ULN

• ER, PR and HER2 status required

• LVEF (MUGA/echo WNL)

• No baseline > 2 neuropathy

• Urine protein: creat ratio < 1.0

• HER2-negative - either IHC 0-1+ or FISH ratio < 2.0

• Hemoglobin > 9 gm/dl

• (FISH testing is required for all HER2 2-3+ tumors by IHC)

Exclusion criteria:

• No Histologically documented adenocarcinoma of the breast

• No-ANC > 1000 cells

• Female; age < 18

• Zubrod PS > 0-1

• Platelets < 100,000

• Stage IV disease

• Total bilirubin > 1.5 ULN

• metastatic disease

• Serum Creatinine > 1.5 gm/dl

• prior systemic therapy for breast cancer or Creat Cl > 30 ml/min

• pregnant or lactating

• Serum ALT > 2.0 ULN baseline > 2 neuropathy

• Urine protein: creat ratio >1.0

• HER2-positive

• Hemoglobin < 9 gm/dl

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bridgeport Hospital	Bridgeport	Connecticut	United States	06610
2	Yale Smilow Cancer Center	New Haven	Connecticut	United States	06519
3	Rhode Island Hsopital	Providence	Rhode Island	United States	02903
4	Women and Infants	Providence	Rhode Island	United States	02905
5	The Miriam Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• William Sikov MD
• Yale University

Investigators

• Principal Investigator: William Sikov, MD, Brown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William Sikov MD, Principle Investigator, Brown University
• ClinicalTrials.gov Identifier: NCT00723125
• Other Study ID Numbers: BrUOG-BR-211A
• First Posted: Jul 28, 2008
• Last Update Posted: Apr 29, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by William Sikov MD, Principle Investigator, Brown University: Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	DDAC: (dose-dense doxorubicin and cyclophosphamide (DDAC)

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)	Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)
Period Title: Overall Study
STARTED	33	27
COMPLETED	15	21
NOT COMPLETED	18	6

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)	Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)	Total of all reporting groups
Overall Participants	33	27	60
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	47.6	45.8	46.8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 97%	27 100%	59 98.3%
>=65 years	1 3%	0 0%	1 1.7%
Sex/Gender, Customized (participants) [Number]
Female	33 100%	27 100%	60 100%
Region of Enrollment (participants) [Number]
United States	33 100%	27 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response Rates at Surgery
Time Frame	at surgery approximately 5 months after initial treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)	Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)
Measure Participants	28	27
Number [participants]	16 48.5%	2 7.4%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Measure of safety and tolerability according to CTCAE version 3.0
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Pts with clinical stage IIA-IIIC BrCa

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks Abraxane: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks Carboplatin: Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10 Avastin: Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)	Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7 Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks Abraxane: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks Carboplatin: Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10 Avastin: Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)
Measure Participants	28	27
Number [participants]	15 45.5%	21 77.8%

Adverse Events

Time Frame	After run-in therapy neo-adjuvantly, throughout treatment and until completion of follow-up (5 years of follow-up) for a total of approximately 6.5 years
Adverse Event Reporting Description	C1 neo: 33 patients enrolled to cohort 1 Neo-adjuvant, only 28 were evaluable C2 neo: 27 enrolled/evaluable cohort 2 Neo-adjuvant C1 DDAC: Of 28 patient evaluable neo-adjuvant, 27 treated DDAC C2 DDAC: Of 27 patients neo-adjuvant, 24 on DDAC C1 Avastin: Of 27 DDAC, 15 Avastin post-op C2 Avastin: Of 24 DDAC, 21 Avastin post-op
Arm/Group Title	Cohort 1 Neo-adjuvant		Cohort 2 Neo-adjuvant		Cohort 1 DDAC		Cohort 2 DDAC		Cohort 1 Adjuvant Post Surgery		Cohort 2 Adjuvant Post Surgery
Arm/Group Description	Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10		Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)		Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles		Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles		Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks		Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks
All Cause Mortality
	Cohort 1 Neo-adjuvant		Cohort 2 Neo-adjuvant		Cohort 1 DDAC		Cohort 2 DDAC		Cohort 1 Adjuvant Post Surgery		Cohort 2 Adjuvant Post Surgery
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1 Neo-adjuvant		Cohort 2 Neo-adjuvant		Cohort 1 DDAC		Cohort 2 DDAC		Cohort 1 Adjuvant Post Surgery		Cohort 2 Adjuvant Post Surgery
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/28 (17.9%)		8/27 (29.6%)		10/27 (37%)		7/24 (29.2%)		2/15 (13.3%)		7/21 (33.3%)
Investigations
gr 3 Nausea, gr 3 vomiting	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 3 nausea, gr 2 infection with noraml ANC, gr 2 HGB, gr 1 glucose	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 2 non-cardiac chest pain, gr 2 anemia	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 3 infection (normal ANC) (cellulitis & pain in buttock - RT infection), gr 1 epistaxis	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
K gr 4,mental status gr 4, ventricular arrythmia gr 4, pneumonia gr 3	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 2 Pleural effusion	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
cr 2, dehydration2, anemia2, weight loss2, fatigue-1, dysgeusia-2, gastritis-2, anorexia-2	1/28 (3.6%)	1	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Mucositis gr 3, fever gr 1, fatigue gr 1	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Acute Kidney Injury gr 2	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 4 GI Bleed (lesion in colon- villious adenoma)	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
FN-gr 1 fever, gr 3 ANC (gr 3 infection)	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
FN (fever gr1, ANC 3, infection3)- however during hospitalization ANC rose to grade 4	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
gr 4 ANC, gr 2 bleeding hemorrhoid, gr 2 rectal pain, dizziness gr 2	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
left groin abcess- gr 2 1/14/14**amended to grade 3**	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
dehydration gr 3, worsening anemia gr 3, diarrhea gr2, anorexia gr 2, ANC 3	0/28 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 3 FN (gr 3 infection, gr 3 ANC), gr 3 mucositis, gr 2 Diarrhea, Gr 2 pain rectal	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 3 periorbital cellulitis associated with chalazia, gr 2 anemia	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 4 ANC	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
anemia 2	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 2 dehydration, gr 2 wt loss, gr 2 anorexia, gr 3 esophagitis, gr 2 mucositis, gr 3 ANC, Gr 4 PLT	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr3 FN, gr3 HGB, Gr2 fatigue, gr2 nausea, gr2 anorexia, gr2 dehydration, gr1 fever, gr1 epistaxis	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
ANC 4, HGB 3, PLT 3	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
weakness gr 4	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
FN gr 3, ANC 3, anemia gr 2, thrombocytopenia gr 3	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
FN gr3, bradycardia gr1, infection gr3, pancytopenia gr3, sore throat gr1, body aches gr1,rigors gr1	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
dehydration2, k3, nausea2, anemia2, cpain2, SOB1, FN, vomiting2, PLT 4, mucositis2, fatigue2	0/28 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
gr 2 odynophagia, gr 2 allergic rxn, gr 2 oral thrush, gr 4 ANC	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
Post Op and Pre-drug- gr 1 fever,gr 2 erythema, gr 2 chills	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
Post op- wound infection gr 2 on DIEP flap	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
FN gr 4 (fever gr 1, ANC 4), cough 2, nasal congestion 2	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
FN (fever gr 1, ANC 4) Anemia 2	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
bleeding from JP drain grade 1	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
FN- fever gr 1, ANC 4	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
FN gr 3 (fever gr 1, ANC gr 3)	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/24 (4.2%)	1	0/15 (0%)	0	0/21 (0%)	0
Post surgery: gr 3 infection	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	1/15 (6.7%)	1	0/21 (0%)	0
gr 4 skin breakdown	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	1/15 (6.7%)	1	0/21 (0%)	0
gr 2 pleural effusion	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	1/15 (6.7%)	1	0/21 (0%)	0
grade 1 fever, gr 3 malignant pleural effusion	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	1/15 (6.7%)	1	0/21 (0%)	0
breast cellulitis gr 3, acute renal injury gr 2, diarrhea gr 1, hemmorrhage GI gr 3	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Post Reconstruction Surgery- infection left breast gr 3	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
post radiation- gr 3 wound complication would dehiscence	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
gr 2 right arm weakness- motor neuropthay, right shoulder pain- r/o TIA	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
secondary malignancy: bladder cancer potentially related to DDAC	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Left breast pain gr 2	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
PE gr 4, fever gr 2	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
post op comp breast cellulitis gr3, migraine gr2	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
related to reconstruction: infection with normal ANC- post complication healing issue (3)	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Cohort 1 Neo-adjuvant		Cohort 2 Neo-adjuvant		Cohort 1 DDAC		Cohort 2 DDAC		Cohort 1 Adjuvant Post Surgery		Cohort 2 Adjuvant Post Surgery
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/28 (100%)		27/27 (100%)		27/27 (100%)		16/24 (66.7%)		5/15 (33.3%)		18/21 (85.7%)
Investigations
WBC	23/28 (82.1%)	23	27/27 (100%)	27	5/27 (18.5%)	5	8/24 (33.3%)	8	0/15 (0%)	0	3/21 (14.3%)	3
ANC	24/28 (85.7%)	24	22/27 (81.5%)	22	4/27 (14.8%)	4	4/24 (16.7%)	4	0/15 (0%)	0	2/21 (9.5%)	2
PLT	25/28 (89.3%)	25	20/27 (74.1%)	20	13/27 (48.1%)	13	2/24 (8.3%)	2	0/15 (0%)	0	0/21 (0%)	0
HGB	27/28 (96.4%)	27	24/27 (88.9%)	24	21/27 (77.8%)	21	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Infection	5/28 (17.9%)	5	6/27 (22.2%)	6	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Myalgias	0/28 (0%)	0	11/27 (40.7%)	11	5/27 (18.5%)	5	0/24 (0%)	0	0/15 (0%)	0	2/21 (9.5%)	2
Creatinine	0/28 (0%)	0	3/27 (11.1%)	3	2/27 (7.4%)	2	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Anorexia	4/28 (14.3%)	4	22/27 (81.5%)	22	5/27 (18.5%)	5	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Wt loss	3/28 (10.7%)	3	5/27 (18.5%)	5	2/27 (7.4%)	2	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Fatigue	20/28 (71.4%)	20	26/27 (96.3%)	26	17/27 (63%)	17	0/24 (0%)	0	0/15 (0%)	0	4/21 (19%)	4
Rash	2/28 (7.1%)	2	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Nausea	12/28 (42.9%)	12	22/27 (81.5%)	22	11/27 (40.7%)	11	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Vomiting	6/28 (21.4%)	6	9/27 (33.3%)	9	3/27 (11.1%)	3	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Mucositis	6/28 (21.4%)	6	16/27 (59.3%)	16	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Rhinitis	5/28 (17.9%)	5	16/27 (59.3%)	16	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Diarrhea	9/28 (32.1%)	9	14/27 (51.9%)	14	2/27 (7.4%)	2	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
LFTs	10/28 (35.7%)	10	12/27 (44.4%)	12	7/27 (25.9%)	7	0/24 (0%)	0	0/15 (0%)	0	3/21 (14.3%)	3
Neurosensory	3/28 (10.7%)	3	17/27 (63%)	17	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Neuromuscular	4/28 (14.3%)	4	6/27 (22.2%)	6	2/27 (7.4%)	2	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Hyponatremia	4/28 (14.3%)	4	5/27 (18.5%)	5	4/27 (14.8%)	4	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Hypokalemia	5/28 (17.9%)	5	7/27 (25.9%)	7	5/27 (18.5%)	5	0/24 (0%)	0	1/15 (6.7%)	1	0/21 (0%)	0
Hypomagnesmia	12/28 (42.9%)	12	4/27 (14.8%)	4	10/27 (37%)	10	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1
Hypocalcemia	5/28 (17.9%)	5	12/27 (44.4%)	12	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Alk-Phos abnormality	4/28 (14.3%)	4	5/27 (18.5%)	5	3/27 (11.1%)	3	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Cough	0/28 (0%)	0	7/27 (25.9%)	7	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
epistaxis or bleeding	13/28 (46.4%)	13	24/27 (88.9%)	24	5/27 (18.5%)	5	12/24 (50%)	12	2/15 (13.3%)	2	7/21 (33.3%)	7
Chest Pain/Bradycardia	0/28 (0%)	0	2/27 (7.4%)	2	2/27 (7.4%)	2	3/24 (12.5%)	3	0/15 (0%)	0	0/21 (0%)	0
HTN	3/28 (10.7%)	3	3/27 (11.1%)	3	3/27 (11.1%)	3	0/24 (0%)	0	2/15 (13.3%)	2	7/21 (33.3%)	7
SOB	3/28 (10.7%)	3	3/27 (11.1%)	3	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Proteinuria	0/28 (0%)	0	3/27 (11.1%)	3	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	3/21 (14.3%)	3
Ocular	0/28 (0%)	0	13/27 (48.1%)	13	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	0/21 (0%)	0
Hyperbili	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/24 (0%)	0	0/15 (0%)	0	1/21 (4.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.