Neo-adjuvant Gemcitabine, Epirubicin, ABI-007 (GEA) in Locally Advanced or Inflammatory Breast Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00193206
• Collaborator: Eli Lilly and Company (Industry), Celgene Corporation (Industry)
• Enrollment: 123
• Locations: 13
• Arm: 1
• Duration (Months): 44
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

In this trial we will evaluate ABI-007 with gemcitabine and epirubicin, utilizing the biweekly pegfilgrastim support, in order to further improve upon the effectiveness and favorable toxicity of this triplet.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Gemcitabine; Drug: Epirubicin; Drug: Albumin-bound Paclitaxel	Phase 2

Detailed Description

Upon determination of eligibility, patients will be receive both induction neo-adjuvant regimen and a postoperative adjuvant regimen:

Induction Neo-adjuvant: Epirubicin + Gemcitabine + ABI-007 + Pegfilgrastim

Postoperative Adjuvant: Gemcitabine + ABI-007 + Pegfilgrastim

Upon completion of chemotherapy, all ER and/or PR+ patients will receive Tamoxifen or an aromatase inhibitor at physician discretion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Dose Dense Neo-adjuvant Gemcitabine, Epirubicin, ABI-007 (GEA) in Locally Advanced or Inflammatory Breast Cancer
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m2, epirubicin 50 mg/m2, and albumin-bound paclitaxel 175 mg/m2 intravenously administered at 14-day intervals. Following neoadjuvant chemotherapy, patients underwent either mastectomy or breast conservation surgery; pathologic response to treatment was assessed. Postoperatively, patients received 4 doses of gemcitabine 2000 mg/m2 with albumin-bound paclitaxel 220 mg/m2 at 14-day intervals. Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy.

Drug: Gemcitabine; Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles; Other Names: Systemic therapy Gemzar ; Drug: Epirubicin; Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles; Other Names: Systemic therapy Ellence ; Drug: Albumin-bound Paclitaxel; ABI-007 175 mg/m2 D1 q 14 days x 6 cycles; Other Names: Systemic therapy ABI-007 Abraxane

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response [18 months]

   For the purpose of this study, a pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast (pT0) and axillary lymph nodes (pN0), gross or microscopic, in the sample removed at the time of surgical resection. Residual ductal or lobular carcinoma in situ was not considered in pCR assessments. Percentage of participants who experienced pCR is reported.

Secondary Outcome Measures

1. Clinical Response Rates [18 months]

   Clinical response rate is defined as percentage of patients whose disease decreased (Partial response - PR) and/or disappeared (Complete response - CR) after treatment). Clinical tumor response was defined as complete if there was no clinical evidence of palpable tumor in either the breast or axilla at the time of surgery. Reduction of total tumor size >50 % at the time surgery was considered a clinical partial response. Evaluations are based on Response Evaluation Criteria in Solid Tumors (RECIST)

2. Time to Disease Progression [36 months]

   Time to progression is the length of time from the start of treatment until the disease progressed. Progressive disease is defined as an increase of >25% in the total calculated product of the tumor's measurements or development of a new lesion. Evaluations are based on Response Evaluation Criteria in Solid Tumors (RECIST)

3. Rates of Breast Preservation [18 months]

   Number of patients who underwent breast conservation after neo adjuvant chemotherapy

Eligibility Criteria

Criteria

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

Inclusion Criteria:

To be included in this study, you must meet the following criteria:

• Locally advanced/inflammatory adenocarcinoma of the breast

• 18 years of age or older

• Normal heart function

• Able to perform activities of daily living with minimal assistance

• No prior chemotherapy for breast cancer

• Adequate bone marrow, liver and kidney function

• No evidence or history of significant cardiovascular abnormalities

• Sentinel node or axillary dissection

• Sign an informed consent form

Exclusion Criteria:

You cannot participate in this study if any of the following apply to you:

• Pregnant or breast feeding

• History of heart disease with congestive heart failure

• Heart attack within the previous 6 months

• Prior chemotherapy or hormone therapy for breast cancer

• History of active uncontrolled infection

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Integrated Community Oncology Network	Jacksonville	Florida	United States	32256
3	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida	United States	33805
4	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
5	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
6	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
7	Hematology Oncology Life Center	Alexandria	Louisiana	United States	71301
8	Mercy Hospital	Portland	Maine	United States	04101
9	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
10	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
11	Chattanooga Oncology and Hematology Associates	Chattanooga	Tennessee	United States	37404
12	Tennessee Oncology	Nashville	Tennessee	United States	37203
13	Peninsula Cancer Institute	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Eli Lilly and Company
• Celgene Corporation

Investigators

• Principal Investigator: Denise A. Yardley, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

• Yardley DA, Zubkus J, Daniel B, Inhorn R, Lane CM, Vazquez ER, Naot Y, Burris HA 3rd, Hainsworth JD. A phase II trial of dose-dense neoadjuvant gemcitabine, epirubicin, and albumin-bound paclitaxel with pegfilgrastim in the treatment of patients with locally advanced breast cancer. Clin Breast Cancer. 2010 Oct 1;10(5):367-72. doi: 10.3816/CBC.2010.n.048.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00193206
• Other Study ID Numbers: SCRI BRE 73
• First Posted: Sep 19, 2005
• Last Update Posted: Nov 23, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by SCRI Development Innovations, LLC: Locally Advanced Breast Cancer; Inflammatory Breast Cancer; Breast Cancer; Abraxane; nab Paclitaxel; Epirubicin; Gemcitabine; Gemzar
• Additional relevant MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Epirubicin

Study Results

Participant Flow

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Period Title: Preoperative Therapy
STARTED	123
COMPLETED	116
NOT COMPLETED	7
Period Title: Preoperative Therapy
STARTED	116
COMPLETED	116
NOT COMPLETED	0
Period Title: Preoperative Therapy
STARTED	116
COMPLETED	102
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Overall Participants	123
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	123 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	123 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response
Description	For the purpose of this study, a pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast (pT0) and axillary lymph nodes (pN0), gross or microscopic, in the sample removed at the time of surgical resection. Residual ductal or lobular carcinoma in situ was not considered in pCR assessments. Percentage of participants who experienced pCR is reported.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

7 patients did not complete the study. Only the patients who had surgical procedures following neoadjuvant chemotherapy were included in the analysis as pathologic complete response is assessing the gross or microscopic response in the tissue sample resected at the time of surgery.

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Measure Participants	116
Count of Participants [Participants]	23 18.7%

2. Secondary Outcome

Title	Clinical Response Rates
Description	Clinical response rate is defined as percentage of patients whose disease decreased (Partial response - PR) and/or disappeared (Complete response - CR) after treatment). Clinical tumor response was defined as complete if there was no clinical evidence of palpable tumor in either the breast or axilla at the time of surgery. Reduction of total tumor size >50 % at the time surgery was considered a clinical partial response. Evaluations are based on Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients who received neoadjuvant chemotherapy

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Measure Participants	123
Count of Participants [Participants]	109 88.6%

3. Secondary Outcome

Title	Time to Disease Progression
Description	Time to progression is the length of time from the start of treatment until the disease progressed. Progressive disease is defined as an increase of >25% in the total calculated product of the tumor's measurements or development of a new lesion. Evaluations are based on Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Measure Participants	123
Median (Full Range) [months]	13.7

4. Secondary Outcome

Title	Rates of Breast Preservation
Description	Number of patients who underwent breast conservation after neo adjuvant chemotherapy
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

patients who had completed all 6 prescribed doses of neoadjuvant chemotherapy

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
Measure Participants	116
Count of Participants [Participants]	26 21.1%

Adverse Events

Arm/Group Title	Intervention
Arm/Group Description	Systemic Therapy ABI-007 : ABI-007 175 mg/m2 D1 q 14 days x 6 cycles Epirubicin : Epirubicin 50 mg/m2 D1 q 14 days x 6 cycles Gemcitabine : Gemcitabine 2000 mg/m2 IV D1 q 14 days x 6 cycles
All Cause Mortality
	Intervention
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	22/123 (17.9%)
Cardiac disorders
Cardiac Ischemia/Infarction	1/123 (0.8%)	1
Pain - Chest	2/123 (1.6%)	2
Gastrointestinal disorders
Dehydration	2/123 (1.6%)	2
General disorders
Death	1/123 (0.8%)	1
Weakness	1/123 (0.8%)	1
Hepatobiliary disorders
Pain - Liver	1/123 (0.8%)	1
Infections and infestations
Infection - Skin	3/123 (2.4%)	3
Infection - Gastrointestinal	1/123 (0.8%)	1
Infection - Vein	2/123 (1.6%)	2
Infection - Pneumonia	1/123 (0.8%)	1
Infection - Skin	3/123 (2.4%)	4
Musculoskeletal and connective tissue disorders
Fracture	2/123 (1.6%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	1/123 (0.8%)	1
Psychiatric disorders
Neurology - Other	1/123 (0.8%)	1
Vascular disorders
Thrombosis/Thrombus/Embolism	2/123 (1.6%)	2
Other (Not Including Serious) Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	41/123 (33.3%)
Blood and lymphatic system disorders
Neutrophils	13/123 (10.6%)
Platelets	7/123 (5.7%)
General disorders
Fatigue	7/123 (5.7%)
Musculoskeletal and connective tissue disorders
Arthralgia/Myalgia	8/123 (6.5%)
Vascular disorders
Thrombosis/Thrombus/Embolism	6/123 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.