Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00093808
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 47
• Locations: 147
• Arm: 1
• Duration (Months): 105
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor killing substances to them without harming normal cells. Giving capecitabine and vinorelbine together with trastuzumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving capecitabine and vinorelbine together with trastuzumab works in treating patients who have metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab; Drug: capecitabine; Drug: vinorelbine tartrate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the overall response rate in patients with HER2/neu-overexpressing metastatic breast cancer treated with first- or second-line therapy comprising capecitabine, vinorelbine, and trastuzumab (Herceptin^®).

Secondary

• Determine the time to disease progression, duration of response, and overall survival of patients treated with this regimen.

• Determine the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Capecitabine in Combination With Vinorelbine and Trastuzumab for the First- or Second-LineTreatment of HER2+ Metastatic Breast Cancer
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: capecitabine + vinorelbine + trastuzumab Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Biological: trastuzumab; Drug: capecitabine; Drug: vinorelbine tartrate

Outcome Measures

Primary Outcome Measures

1. Confirmed Response Rate [Up to 5 years]

   A confirmed tumor response is defined to be either a Complete Response (CR) or Partial Response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart. All patients meeting the eligibility criteria who have signed a consent form and initiated study medication will be evaluable for response. The proportion of confirmed tumor responses will be estimated by the number of tumor regressions that meet the RECIST criteria for a confirmed CR or PR divided by the total number of evaluable patients. A 95% confidence interval for the true confirmed response rate will be calculated using the properties of the binomial distribution. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Time to Progression (TTP) [Up to 5 years]

   Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for any evaluations, that patient will be censored for progression of disease at day one post-registration. Otherwise, for patients that do not progress, censoring will occur at the last follow up date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or unequivocal progression of existing non-target lesions.

2. Duration of Response as Measured by RECIST Criteria [Up to 5 years]

   Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a Complete Response (CR) or Partial Response (PR) to the date progression is documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

3. Overall Survival as Assessed by Time [Up to 5 years]

   Overall survival: The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier method.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive breast cancer

• Metastatic disease

• HER2/neu-positive by immunohistochemistry (3+ by HercepTest^™ or equivalent) OR positive for amplification by fluorescent in situ hybridization

• Testing may be performed in the primary tumor or the metastatic site

• Received prior anthracycline or taxane as adjuvant therapy or for metastatic disease

• Measurable disease

• At least one measurable lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan

• The following are considered non-measurable disease:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast disease

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• No bone metastases as the only evidence of metastasis

• Previously treated CNS metastases allowed provided disease has been stable for ≥ the past 3 months

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female or male

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

• Hemoglobin ≥ 8.0 g/dL

• Platelet count ≥ 100,000/mm^3

• No known uncontrolled coagulopathy

Hepatic

• Bilirubin ≤ 3.0 times the upper limit of normal (ULN)

• One of the following must be true:

• AST or ALT ≤ 5 times ULN AND alkaline phosphatase normal

• Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal

• Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• INR ≤ 1.5 times ULN

Renal

• Calcium ≤ 11.5 mg/dL

• Creatinine ≤ 1.5 times ULN

• Creatinine clearance ≥ 30 mL/min

Cardiovascular

• LVEF ≥ 50% by MUGA or echocardiogram

• No clinically significant (i.e., active) cardiac disease

• No congestive heart failure

• No symptomatic coronary artery disease

• No myocardial infarction within the past 12 months

• No cardiac arrhythmia not controlled with medication

Gastrointestinal

• Able to take oral medication

• No lack of physical integrity of the upper gastrointestinal tract

• No clinically significant malabsorption syndrome

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 30 days after study participation

• No history of allergy or hypersensitivity to study drugs, drug product excipients, including polysorbate 80, or chemically similar agents

• No prior unanticipated severe reaction to fluoropyrimidine therapy

• No know hypersensitivity to fluorouracil

• No known dihydropyrimidine dehydrogenase deficiency

• No history of uncontrolled seizures or CNS disorders

• No clinically significant psychiatric disability that would preclude giving informed consent or study compliance

• No other serious uncontrolled infection or disease

• No other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix, or contralateral breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior adjuvant trastuzumab (Herceptin^®) allowed as adjuvant or first-line therapy for metastatic disease

• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics

• No more than 1 prior chemotherapy regimen in the advanced or metastatic (non-adjuvant) setting

• No prior continuous (≥ 24 hours) fluorouracil infusion

• No prior capecitabine

• No prior oral fluoropyrimidines (e.g., eniluracil and fluorouracil, uracil and tegafur, S1, or emitefur)

Endocrine therapy

• At least 1 day since prior hormonal therapy

• No concurrent hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy to the axial skeleton (i.e., skull, spinal column, sternum, or ribs)

• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery

• No prior organ allografts requiring immunosuppressive therapy

Other

• More than 4 weeks since prior investigational drugs

• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)

• No concurrent allopurinol, metronidazole, or cimetidine

• No other concurrent cytotoxic agents

• No other concurrent investigational drugs

• No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
4	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
5	Graham Hospital	Canton	Illinois	United States	61520
6	Memorial Hospital	Carthage	Illinois	United States	62321
7	Eureka Community Hospital	Eureka	Illinois	United States	61530
8	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
9	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
10	Mason District Hospital	Havana	Illinois	United States	62644
11	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
12	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
13	McDonough District Hospital	Macomb	Illinois	United States	61455
14	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
15		Moline	Illinois	United States	61265
16	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
17	Community Cancer Center	Normal	Illinois	United States	61761
18	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
19	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
20	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
21	Proctor Hospital	Peoria	Illinois	United States	61614
22	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
23	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
24	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
25	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
26	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
27	Perry Memorial Hospital	Princeton	Illinois	United States	61356
28	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
29	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
30	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
31	Elkhart General Hospital	Elkhart	Indiana	United States	46515
32	Howard Community Hospital	Kokomo	Indiana	United States	46904
33	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
34	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
35	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
36	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
37	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
38	McFarland Clinic, PC	Ames	Iowa	United States	50010
39		Bettendorf	Iowa	United States	52722
40	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
41	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
42	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
43	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
44	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
45	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
46	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
47	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
48	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
49	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
50	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
51	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
52	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
53	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
54	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
55	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
56	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
57	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
58	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
59	Hurley Medical Center	Flint	Michigan	United States	48503
60	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
61	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
62	Foote Memorial Hospital	Jackson	Michigan	United States	49201
63	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
64	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
65	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
66	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
67	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
68	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
69	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
70	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
71	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
72	St. John Macomb Hospital	Warren	Michigan	United States	48093
73		Alexandria	Minnesota	United States	56308
74	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
75	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
76	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
77	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
78	CCOP - Duluth	Duluth	Minnesota	United States	55805
79	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
80	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
81		Fergus Falls	Minnesota	United States	56537
82	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
83	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
84	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
85	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
86	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
87	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
88	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
89	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
90	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
91	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
92	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
93	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
94	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
95	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
96	United Hospital	Saint Paul	Minnesota	United States	55102
97	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
98	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
99	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
100	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
101	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
102	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
103	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
104	Immanuel Medical Center	Omaha	Nebraska	United States	68122
105	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
106	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
107	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
108	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
109	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
110	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
111	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
112	MeritCare Broadway	Fargo	North Dakota	United States	58122
113	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
114	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
115	Lima Memorial Hospital	Lima	Ohio	United States	45804
116	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
117	St. Luke's Hospital	Maumee	Ohio	United States	43537
118	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
119	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
120	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
121	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
122	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
123	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
124	Toledo Hospital	Toledo	Ohio	United States	43606
125	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
126	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
127	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
128	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
129	Fulton County Health Center	Wauseon	Ohio	United States	43567
130	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
131	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
132	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
133	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
134	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
135	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
136	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
137	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
138	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
139	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
140	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
141	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
142	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
143	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
144	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
145	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
146	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
147	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Winston Tan, MD, FACP, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00093808
• Other Study ID Numbers: NCCTG-N0337; NCI-2012-02625; CDR0000390344
• First Posted: Oct 8, 2004
• Last Update Posted: Mar 6, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: recurrent breast cancer; stage IV breast cancer; male breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine; Trastuzumab; Vinorelbine

Study Results

Participant Flow

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Period Title: Overall Study
STARTED	47
COMPLETED	45
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Overall Participants	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	46 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Confirmed Response Rate
Description	A confirmed tumor response is defined to be either a Complete Response (CR) or Partial Response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart. All patients meeting the eligibility criteria who have signed a consent form and initiated study medication will be evaluable for response. The proportion of confirmed tumor responses will be estimated by the number of tumor regressions that meet the RECIST criteria for a confirmed CR or PR divided by the total number of evaluable patients. A 95% confidence interval for the true confirmed response rate will be calculated using the properties of the binomial distribution. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients who completed the study were included in all analyses unless otherwise specified.

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Measure Participants	45
Number (95% Confidence Interval) [proportion of patients]	0.67

2. Secondary Outcome

Title	Time to Progression (TTP)
Description	Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for any evaluations, that patient will be censored for progression of disease at day one post-registration. Otherwise, for patients that do not progress, censoring will occur at the last follow up date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or unequivocal progression of existing non-target lesions.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients who completed the study or deemed a protocol violation were included in all analyses unless otherwise specified.

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Measure Participants	46
Median (95% Confidence Interval) [months]	11.3

3. Secondary Outcome

Title	Duration of Response as Measured by RECIST Criteria
Description	Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a Complete Response (CR) or Partial Response (PR) to the date progression is documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients who completed the study or deemed a protocol violation were included in all analyses unless otherwise specified.

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Measure Participants	46
Median (95% Confidence Interval) [months]	13.2

4. Secondary Outcome

Title	Overall Survival as Assessed by Time
Description	Overall survival: The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier method.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients who completed the study or deemed a protocol violation were included in all analyses unless otherwise specified.

Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
Measure Participants	46
Median (95% Confidence Interval) [months]	28.5

Adverse Events

Time Frame	Adverse events are collected 2 weeks prior to registration, at each evaluation , and at end of treatment during the Active-Monitoring Phase; up to 5 years post registration.
Adverse Event Reporting Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until June 30, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning July 1, 2011. Adverse events data collected for patients who received and completed at least one cycle of treatment are reported below (i.e. for patients who completed the study or deemed a protocol violation).
Arm/Group Title	Capecitabine + Vinorelbine + Trastuzumab
Arm/Group Description	Treatment followed a 21-day cycle. Capecitabine was administered orally twice daily at a dose of 825 mg/m^2 on days 1 to 14, vinorelbine was administered intravenously (IV) at a dose of 25 mg/m^2 on days 1 and 8 every 3 weeks, and trastuzumab was administered IV at a dose of 6 mg/kg on day 1 of every 3-week cycle (except cycle 1, when patients were given a loading dose of 8 mg/kg).
All Cause Mortality
	Capecitabine + Vinorelbine + Trastuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Capecitabine + Vinorelbine + Trastuzumab
	Affected / at Risk (%)	# Events
Total	9/46 (19.6%)
Blood and lymphatic system disorders
Febrile neutropenia	1/46 (2.2%)	1
Cardiac disorders
Cardiac disorder	1/46 (2.2%)	1
Gastrointestinal disorders
Diarrhea	1/46 (2.2%)	1
Upper gastrointestinal hemorrhage	1/46 (2.2%)	1
General disorders
Chest pain	1/46 (2.2%)	1
Fatigue	1/46 (2.2%)	1
Investigations
Neutrophil count decreased	2/46 (4.3%)	2
Platelet count decreased	1/46 (2.2%)	1
Metabolism and nutrition disorders
Anorexia	1/46 (2.2%)	1
Dehydration	1/46 (2.2%)	1
Serum potassium increased	1/46 (2.2%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Capecitabine + Vinorelbine + Trastuzumab
	Affected / at Risk (%)	# Events
Total	46/46 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	11/46 (23.9%)	23
Hemolysis	1/46 (2.2%)	1
Cardiac disorders
Cardiac disorder	1/46 (2.2%)	1
Left ventricular dysfunction	2/46 (4.3%)	2
Eye disorders
Cataract	1/46 (2.2%)	1
Watering eyes	2/46 (4.3%)	9
Gastrointestinal disorders
Abdominal pain	5/46 (10.9%)	9
Constipation	5/46 (10.9%)	6
Diarrhea	30/46 (65.2%)	113
Dyspepsia	3/46 (6.5%)	4
Ear, nose and throat examination abnormal	2/46 (4.3%)	2
Enteritis	1/46 (2.2%)	1
Esophagitis	1/46 (2.2%)	1
Gastrointestinal disorder	2/46 (4.3%)	2
Lower gastrointestinal hemorrhage	2/46 (4.3%)	2
Mucositis oral	8/46 (17.4%)	10
Nausea	8/46 (17.4%)	9
Toothache	1/46 (2.2%)	1
Vomiting	5/46 (10.9%)	8
General disorders
Chest pain	1/46 (2.2%)	1
Edema limbs	2/46 (4.3%)	2
Fatigue	45/46 (97.8%)	356
Fever	1/46 (2.2%)	1
Injection site reaction	6/46 (13%)	19
Visceral edema	1/46 (2.2%)	1
Immune system disorders
Cytokine release syndrome	1/46 (2.2%)	1
Hypersensitivity	3/46 (6.5%)	3
Infections and infestations
Bladder infection	1/46 (2.2%)	1
Infection	2/46 (4.3%)	2
Lip infection	1/46 (2.2%)	1
Nail infection	1/46 (2.2%)	1
Pneumonia	2/46 (4.3%)	2
Skin infection	2/46 (4.3%)	2
Tooth infection	1/46 (2.2%)	1
Upper respiratory infection	1/46 (2.2%)	1
Injury, poisoning and procedural complications
Vascular access complication	1/46 (2.2%)	1
Investigations
Alanine aminotransferase increased	1/46 (2.2%)	2
Alkaline phosphatase increased	1/46 (2.2%)	2
Aspartate aminotransferase increased	1/46 (2.2%)	1
Blood bilirubin increased	3/46 (6.5%)	5
Creatinine increased	9/46 (19.6%)	13
INR increased	1/46 (2.2%)	2
Leukocyte count decreased	11/46 (23.9%)	32
Lipase increased	1/46 (2.2%)	1
Lymphocyte count decreased	1/46 (2.2%)	1
Neutrophil count decreased	39/46 (84.8%)	196
Platelet count decreased	8/46 (17.4%)	38
Weight loss	1/46 (2.2%)	1
Metabolism and nutrition disorders
Anorexia	6/46 (13%)	8
Blood glucose increased	2/46 (4.3%)	7
Dehydration	4/46 (8.7%)	5
Serum calcium decreased	3/46 (6.5%)	5
Serum potassium decreased	4/46 (8.7%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	4/46 (8.7%)	7
Back pain	3/46 (6.5%)	3
Bone pain	25/46 (54.3%)	136
Fibrosis	2/46 (4.3%)	8
Muscle weakness	2/46 (4.3%)	2
Muscle weakness lower limb	1/46 (2.2%)	5
Myalgia	27/46 (58.7%)	139
Nervous system disorders
Dizziness	3/46 (6.5%)	3
Dysgeusia	2/46 (4.3%)	8
Headache	3/46 (6.5%)	7
Neuralgia	1/46 (2.2%)	2
Peripheral motor neuropathy	9/46 (19.6%)	23
Peripheral sensory neuropathy	32/46 (69.6%)	298
Syncope	1/46 (2.2%)	1
Psychiatric disorders
Anxiety	1/46 (2.2%)	9
Depression	2/46 (4.3%)	2
Insomnia	1/46 (2.2%)	12
Renal and urinary disorders
Proteinuria	1/46 (2.2%)	1
Reproductive system and breast disorders
Vaginal pain	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/46 (2.2%)	6
Dyspnea	6/46 (13%)	20
Hypoxia	1/46 (2.2%)	2
Pleural effusion	1/46 (2.2%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/46 (2.2%)	2
Dry skin	2/46 (4.3%)	3
Hand-and-foot syndrome	25/46 (54.3%)	202
Nail disorder	1/46 (2.2%)	1
Rash desquamating	11/46 (23.9%)	31
Vascular disorders
Hot flashes	1/46 (2.2%)	2
Hypotension	1/46 (2.2%)	1
Lymphedema	1/46 (2.2%)	3
Thrombosis	2/46 (4.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.