Preoperative Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in HER-2 Positive Breast Cancer

• Sponsor: Eric Winer, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00148668
• Collaborator: Dana-Farber Cancer Institute (Other), Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other), Beth Israel Deaconess Medical Center (Other), Yale University (Other)
• Enrollment: 81
• Locations: 4
• Arms: 2
• Duration (Months): 92
• Patients Per Site: 20.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to find out what effects the preoperative combination therapies of herceptin/navelbine or herceptin/taxotere/carboplatin will have on patients with early stage HER-2 positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Herceptin; Drug: Navelbine; Drug: Taxotere; Drug: Carboplatin	Phase 2

Detailed Description

Before starting treatment, a clip will be placed via catheter into the tumor bed, so the surgeon can locate the site of the tumor. During clip placement, tissue biopsy will be taken of the tumor. One to two weeks after the first dose of herceptin another biopsy will be performed.

Patients will be placed into one of 2 arms.

• Arm 1 receives 12 weeks of herceptin and navelbine. Arm 2 receives 4 cycles of taxotere/carboplatin/herceptin.

• Arm 2 participants will also receive neulasta (growth factor support) on day 2 of each cycle.

Phase A of Arm 1 is one dose of herceptin followed by an MRI of the affected breast and a second biopsy 1-2 weeks following this dose. Phase B of Arm 1 begins on week 3 and ends on week 14 and involves weekly injections of herceptin and navelbine. Surgery will take place a minimum of 3 weeks after the patients last dose of herceptin and navelbine.

Phase A of Arm 2 is one dose of herceptin followed by an MRI of the affected breast and second biopsy 1-2 weeks following this dose. Phase B of Arm 2 begins on week 3 and ends on week 14 and involves herceptin weekly, taxotere and carboplatin every 3 weeks. Surgery will take place a minimum of 3 weeks after the patients last dose of herceptin, taxotere and carboplatin.

Blood tests will be performed every 3 weeks during pre-operative treatment and every 6 months after surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Preoperative Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Early Stage, HER-2 Positive Breast Cancer
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 Herceptin/navelbine	Drug: Herceptin; One dose given followed by an MRI, then weekly injections beginning week 3 and ending week 14.; Other Names: Trastuzumab ; Drug: Navelbine; Weekly injections given starting week 3 and ending week 14; Other Names: vinorelbine
Active Comparator: Arm 2 Taxotere/carboplatin/herceptin	Drug: Herceptin; One dose given followed by an MRI, then weekly injections beginning week 3 and ending week 14.; Other Names: Trastuzumab ; Drug: Taxotere; Given every three weeks starting week 3 and ending on week 14; Other Names: docetaxel ; Drug: Carboplatin; Given every three weeks starting week 3 and ending on week 14; Other Names: paraplatin

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response After Preoperative Therapy With Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Patients With HER-2 Positive Early Breast Cancer [12 weeks]

   Pathological Complete Response is defined as the complete disappearance of invasive tumor in the breast at the time of surgery

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with stage II or III breast cancer

• HER-2 positive tumors

• Older than 18 years of age

• Eastern Cooperative Oncology Group (ECOG) Performance Status of greater or equal to 1.

• ANC > 1,500/mm3

• Hemoglobin > 9gm/dl

• Platelets > 100,000mm3

• Creatinine < 2mg/dl

• Glucose < 200mg/dl

• Bilirubin < 1.5 x ULN

Exclusion Criteria:

• Previous treatment with herceptin, taxanes, doxorubicin or other anthracycline-type therapy, navelbine, or platinum-based therapy.

• Pregnant or breast-feeding women

• Serious illness, or medical or psychiatric condition

• Uncontrolled infections

• Active or severe cardiovascular or pulmonary disease

• Patients with left ventricular ejection fraction < 50%

• Peripheral neuropathy of any etiology that exceeds grade 1

• Prior history of malignancy

• Uncontrolled diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06520
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Eric Winer, MD
• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Yale University

Investigators

• Principal Investigator: Eric Winer, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eric Winer, MD, Chief Division of Women's Cancers, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00148668
• Other Study ID Numbers: 03-311
• First Posted: Sep 8, 2005
• Last Update Posted: Apr 9, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Eric Winer, MD, Chief Division of Women's Cancers, Dana-Farber Cancer Institute: HER-2 Positive Breast Cancer; herceptin; navelbine; taxotere; carboplatin; Early stage Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Carboplatin; Docetaxel; Trastuzumab; Vinorelbine

Study Results

Participant Flow

Recruitment Details	A total of 81 patients were enrolled on the study between 12/2003 and 8/2008.

Arm/Group Title	Herceptin/Navelbine	Taxotere/Carboplatin/Herceptin
Arm/Group Description	Herceptin( 2mg/kg)navelbine (25mg/kg2) x 12 weeks	Taxotere (75mg/kg2)/carboplatin (AUC6)/herceptin(2mg/kg)[TC q 3 weeks/H q 1 wk) x 4 cycles
Period Title: Overall Study
STARTED	41	40
COMPLETED	41	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Herceptin/navelbine	Taxotere/carboplatin/herceptin	Total of all reporting groups
Overall Participants	41	40	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.8 (12.6)	48.1 (8.5)	48 (10.7)
Sex: Female, Male (Count of Participants)
Female	41 100%	40 100%	81 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	41 100%	40 100%	81 100%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response After Preoperative Therapy With Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Patients With HER-2 Positive Early Breast Cancer
Description	Pathological Complete Response is defined as the complete disappearance of invasive tumor in the breast at the time of surgery
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Please Note that in Arm 2, the number of participants analyzed is equal to 39, which differs from the Number of Participants reported in the baseline measure (N= 40) because one participant withdrew her consent, so was not evaluable.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Herceptin/navelbine	Taxotere/carboplatin/herceptin
Measure Participants	41	39
Number [percentage of participants]	17 41.5%	31 77.5%

Adverse Events

Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Herceptin/navelbine		Taxotere/carboplatin/herceptin
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/41 (12.2%)		5/40 (12.5%)
Blood and lymphatic system disorders
Neutropenia	4/41 (9.8%)	4	4/40 (10%)	4
Febrile Neutropenia	0/41 (0%)	0	1/40 (2.5%)	1
Hepatobiliary disorders
SGPT (ALT)	1/41 (2.4%)	1	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/41 (65.9%)		25/40 (62.5%)
Blood and lymphatic system disorders
Dehydration	0/41 (0%)	0	2/40 (5%)	2
Gastrointestinal disorders
Diarrhea	1/41 (2.4%)	1	2/40 (5%)	2
Anorexia	0/41 (0%)	0	2/40 (5%)	2
General disorders
Fatigue	1/41 (2.4%)	1	2/40 (5%)	2
Hepatobiliary disorders
SGOT (AST)	3/41 (7.3%)	3	0/40 (0%)	0
SGPT (ALT)	4/41 (9.8%)	4	0/40 (0%)	0
Immune system disorders
Leukocytes	6/41 (14.6%)	6	7/40 (17.5%)	7
Neutropenia	11/41 (26.8%)	11	5/40 (12.5%)	5
Febrile Neutropenia	1/41 (2.4%)	1	2/40 (5%)	2
Reproductive system and breast disorders
Irregular Menses	0/41 (0%)	0	3/40 (7.5%)	3

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.