Trial Outcomes & Findings for Phase II NCT (Neoadjuvant Chemotherapy) w/ Weekly Abraxane in Combination With Carboplatin & Bevacizumab in Breast Cancer (NCT NCT00675259)

NCT ID: NCT00675259

Last Updated: 2018-07-24

Results Overview

pCR was defined as the absence of viable invasive tumor cells in the surgical breast specimen and axillary lymph nodes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: every 4 weeks
• Results posted on: 2018-07-24

Participant Flow

Participant milestones

Measure	Neoadjuvant, Surgery, Adjuvant Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT (Neoadjuvant chemotherapy). Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.
Overall Study STARTED	33
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II NCT (Neoadjuvant Chemotherapy) w/ Weekly Abraxane in Combination With Carboplatin & Bevacizumab in Breast Cancer

Baseline characteristics by cohort

Measure	Neoadjuvant, Surgery, Adjuvant n=33 Participants Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT (Neoadjuvant chemotherapy). Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.
Age, Continuous	48 years n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	33 patients n=5 Participants
Menopausal status Premenopausal	21 patients n=5 Participants
Menopausal status Postmenopausal	12 patients n=5 Participants
Receptor status (all HER2/neu negative) Triple negative	12 patients n=5 Participants
Receptor status (all HER2/neu negative) ER and PR positive	21 patients n=5 Participants
Axillary lymph node status before NCT Positive by core biopsy	15 patients n=5 Participants
Axillary lymph node status before NCT Positive by SLNB	4 patients n=5 Participants
Axillary lymph node status before NCT Negative by core biopsy	5 patients n=5 Participants
Axillary lymph node status before NCT Negative by SLNB	8 patients n=5 Participants
Axillary lymph node status before NCT Not evaluated	1 patients n=5 Participants

PRIMARY outcome

Timeframe: every 4 weeks

Population: Includes patients with triple negative breast cancer and ER+/PR+ breast cancer.

pCR was defined as the absence of viable invasive tumor cells in the surgical breast specimen and axillary lymph nodes.

Outcome measures

Measure	Neoadjuvant, Surgery, Adjuvant n=33 Participants Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT. Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.	Patients With pCR Pathologic complete response (pCR)	Patients With Hormone-responsive BC Hormone-responsive breast cancer (BC)
Number of Patients With Pathologic Complete Response (pCR)	6 patients	—	—

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: all grade 3 adverse events

Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0

Outcome measures

Measure	Neoadjuvant, Surgery, Adjuvant n=33 Participants Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT. Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.	Patients With pCR Pathologic complete response (pCR)	Patients With Hormone-responsive BC Hormone-responsive breast cancer (BC)
Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab hypersensitivity reaction	1 patients	—	—
Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab hypertension	2 patients	—	—
Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab infection at mastectomy site	1 patients	—	—

SECONDARY outcome

Timeframe: after 2 cycles of therapy

Population: Data only available for 20 of the 28 evaluable patients

Relative angiogenic volume (AV) was defined as the ratio of AV to the geometric volume of the tumor in the breast.

Outcome measures

Measure	Neoadjuvant, Surgery, Adjuvant n=20 Participants Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT. Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.	Patients With pCR Pathologic complete response (pCR)	Patients With Hormone-responsive BC Hormone-responsive breast cancer (BC)
Evaluation of Dynamic Contrast-enhanced Magnetic Resonance Imaging in Assessing pCR at Baseline and After 2 Cycles of Neoadjuvant Therapy Baseline DCE-MRI	0.65 ratio Standard Deviation 0.18	—	—
Evaluation of Dynamic Contrast-enhanced Magnetic Resonance Imaging in Assessing pCR at Baseline and After 2 Cycles of Neoadjuvant Therapy Relative AV at end of cycle 2	.4 ratio Standard Deviation .33	—	—

SECONDARY outcome

Timeframe: prior to surgery

Population: LZTS1 expression in breast cancer cells collected prior to NCT was assessed in 27 patients who had evaluable core biopsies.

LZTS1 expression in breast cancer cells collected prior to NCT

Outcome measures

Measure	Neoadjuvant, Surgery, Adjuvant n=11 Participants Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT. Use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.	Patients With pCR n=5 Participants Pathologic complete response (pCR)	Patients With Hormone-responsive BC n=16 Participants Hormone-responsive breast cancer (BC)
Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry 0	2 patients	2 patients	6 patients
Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry +1	0 patients	0 patients	2 patients
Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry +2	3 patients	2 patients	2 patients
Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry +3	6 patients	1 patients	6 patients

Adverse Events

Toxicities During Neoadjuvant Chemotherapy

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Toxicities During Neoadjuvant Chemotherapy n=33 participants at risk
Blood and lymphatic system disorders Leukopenia	78.8% 26/33 • Number of events 26 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Blood and lymphatic system disorders Anemia	48.5% 16/33 • Number of events 16 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Blood and lymphatic system disorders Thrombocytopenia	39.4% 13/33 • Number of events 13 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Blood and lymphatic system disorders Neutropenia	87.9% 29/33 • Number of events 29 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Injury, poisoning and procedural complications Wound Complications	9.1% 3/33 • Number of events 3 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
General disorders Fatigue	84.8% 28/33 • Number of events 28 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Gastrointestinal disorders Nausea	24.2% 8/33 • Number of events 8 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Infections and infestations Infection with normal ANC	24.2% 8/33 • Number of events 8 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Nervous system disorders Peripherial neuropathy	24.2% 8/33 • Number of events 8 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Gastrointestinal disorders Constipation	24.2% 8/33 • Number of events 8 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Vascular disorders Hypertension	18.2% 6/33 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Psychiatric disorders Depressed Mood	18.2% 6/33 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Psychiatric disorders Insomnia	36.4% 12/33 • Number of events 12 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Nervous system disorders Headache	36.4% 12/33 • Number of events 12 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	30.3% 10/33 • Number of events 10 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Gastrointestinal disorders Diarrhea	18.2% 6/33 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.
Gastrointestinal disorders Mucositis	12.1% 4/33 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading patients adverse events.

Additional Information

Ewa Mrozek, MD

The Ohio State University

Phone: 614-293-0066

Email: Ewa.mrozek@osumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place