Trial Outcomes & Findings for Phase II Neoadjuvant Trial of Trastuzumab in Combination With Dose-Dense ABI-007 (Abraxane™) (NCT NCT00503750)

Last Updated: 2012-06-25

Results Overview

Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR. Although clinical examination is the primary method of determining response, radiologic assessments (mammogram, ultrasound ± MRI) may be used to confirm response/non-response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

assess at 8 weeks

Results posted on

2012-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Overall Study STARTED	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II Neoadjuvant Trial of Trastuzumab in Combination With Dose-Dense ABI-007 (Abraxane™)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine n=27 Participants Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	49 years n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants

PRIMARY outcome

Timeframe: assess at 8 weeks

Outcome measures

Outcome measures
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine n=27 Participants Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Number of Participants With Complete Pathologic Response.	13 participants

SECONDARY outcome

Timeframe: clinic examination every 2 weeks, evaluated every 3 months for 2 years post-op

Complete clinical response (CCR): complete disappearance of all measurable malignant disease. No new malignant lesion, disease-related symptoms or evidence of non-evaluable disease. Partial response (PR): Reduction by at least 50% of the sum of the products of the longest perpendicular diameters of all measurable lesions. Stable disease (SD): For bidimensionally measurable disease, no decrease or \<25% increase in the sum of the products of the longest perpendicular diameters of all measurable lesions.

Outcome measures

Outcome measures
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine n=27 Participants Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Number of Participants Who Had Complete Clinical Resposnse, Partial Response and Stable Disease. Complete Response	20 participants
Number of Participants Who Had Complete Clinical Resposnse, Partial Response and Stable Disease. Partial Response	7 participants
Number of Participants Who Had Complete Clinical Resposnse, Partial Response and Stable Disease. Stable Disease	0 participants

Adverse Events

Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine

Serious events: 12 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine n=27 participants at risk Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Nervous system disorders Neuropathy	11.1% 3/27
Nervous system disorders Neutropenia	22.2% 6/27
Nervous system disorders Febrile Neutropenia	3.7% 1/27
Blood and lymphatic system disorders Anemia	3.7% 1/27
General disorders Fatigue	3.7% 1/27

Other adverse events

Other adverse events
Measure	Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine n=27 participants at risk Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta®) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Blood and lymphatic system disorders Neuropathy	74.1% 20/27
Nervous system disorders Neutropenia	14.8% 4/27
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/27
General disorders Fatigue	66.7% 18/27
Gastrointestinal disorders Nausea	40.7% 11/27
Musculoskeletal and connective tissue disorders Myalgias/Arthralgias	74.1% 20/27
Hepatobiliary disorders Liver Tests	44.4% 12/27
Skin and subcutaneous tissue disorders Nail changes	11.1% 3/27
Blood and lymphatic system disorders Anemia	51.9% 14/27
General disorders Stomatitis	18.5% 5/27
Blood and lymphatic system disorders Thrombocytopenia	7.4% 2/27
Gastrointestinal disorders Diarrhea	25.9% 7/27
Gastrointestinal disorders Constipation	33.3% 9/27
General disorders Headache	37.0% 10/27

Additional Information

Dr. Ruth O'Regan

Emory University

Phone: 404-778-8808

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place