Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00390455
• Collaborator: (none)
• Enrollment: 295
• Locations: 368
• Arms: 2
• Actual Duration (Months): 93.5
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies fulvestrant and lapatinib to see how well they work compared to fulvestrant and a placebo in treating postmenopausal women with stage III or stage IV breast cancer that is hormone receptor-positive. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of breast cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether fulvestrant is more effective with or without lapatinib in treating breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Estrogen Receptor Positive; HER2 Positive Breast Carcinoma; HER2/Neu Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7	Drug: Fulvestrant; Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Other: Placebo Administration	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To compare the effect, in terms of progression free survival, of the antiestrogen fulvestrant alone with fulvestrant administered in combination with the dual-kinase inhibitor lapatinib for postmenopausal women with estrogen receptor (ER) and/or progesterone receptor (PgR) positive advanced breast cancer.

SECONDARY OBJECTIVES:

1. To compare the effects of fulvestrant alone with fulvestrant and lapatinib on other clinical endpoints, including response rate, response and stable disease rate (complete response [CR] + partial response [PR] + stable disease >= 6 months), duration of response, overall survival, symptom checklist scores, and toxicity.

2. To define predictive markers of clinical activity among women receiving fulvestrant with or without lapatinib.

3. To determine if the clinical benefits for combination of hormonal and growth factor inhibitor therapy are most pronounced in women whose tumors express higher levels of ER, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), phosphorylated protein kinase B (pAkt), and/or phosphorylated mitogen-activated protein kinase 1/2 (pERK1/2).

4. To serologically determine if HER2 extracellular domain (ECD) and EGFR ECD levels can identify patients with a greater likelihood of response and clinical benefit to fulvestrant with or without lapatinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) on days 1-28 and fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of each subsequent course.

ARM II: Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Endocrine Therapy With or Without Inhibition of EGF and HER2 Growth Factor Receptors: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib (GW572016) for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer
• Actual Study Start Date: Sep 15, 2006
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 2, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (lapatinib) Patients receive lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 and 15 of course 1 and on day 1 of each subsequent course. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Fulvestrant; Given IM; Other Names: Faslodex Faslodex(ICI 182,780) ICI 182,780 ICI 182780 ZD9238 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb
Placebo Comparator: Arm II (placebo) Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Fulvestrant; Given IM; Other Names: Faslodex Faslodex(ICI 182,780) ICI 182,780 ICI 182780 ZD9238 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo Administration; Given PO

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years]

   PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria).

Secondary Outcome Measures

1. Objective Tumor Response Rate [Up to 5 years]

   Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.

2. Overall Survival (OS) [Study entry to death or last follow-up, up to 5 years]

   Overall survival was measured as the interval from study entry until death, from any cause, or last contact.

Other Outcome Measures

1. Progression-free Survival for Participants With HER2-negative Tumors [Up to 5 years]

   PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first.

2. Progression-free Survival for Participants With HER2-positive Tumors [Up to 5 years]

   PFS was defined as the interval from study entry until disease progression or death resulting from any cause, whichever occurred first.

3. Objective Tumor Response Rate for Participants With HER2-negative Tumors [Up to 5 years]

   Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.

4. Objective Tumor Response Rate for Participants With HER2-positive Tumors [Up to 5 years]

   Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologic, pathologic or cytologic diagnosis of cancer of the female breast in either primary or metastatic setting; histological documentation of metastatic/recurrent disease is not required if there is unequivocal clinical evidence for recurrence

• Stage IV breast cancer (using American Joint Committee on Cancer [AJCC] criteria, 6th edition), or locally advanced (stage III) breast cancer not considered amenable to curative therapy

• Patients with symptomatic brain metastases or other symptomatic central nervous system (CNS) metastases are not eligible for the study; no screening studies are required among asymptomatic patients; patients with previously treated brain metastases, who are free of symptoms referable to CNS disease and who are > 3 months from treatment for brain metastases are eligible

• Tumors (as determined on pathology from either primary or metastatic sites) must be potentially sensitive to endocrine therapy, defined as expressing estrogen receptor (ER) and/or progesterone receptor (PgR) as determined immunohistochemical methods according to the local institution's standard protocol, >= 1% cells will be considered to be positive

• The protocol has been amended to permit tumors with any HER2 status, though a determination of HER2 status must have been made; patients will be considered to be eligible if HER2 expression is documented by one of the following methods:

• Immunohistochemistry (IHC) 0 (i.e., negative), 1+, 2+, or 3+ levels of expression, or

• Gene amplification (fluorescent in situ hybridization [FISH]) positive or negative

• Patients must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed tomography (CT) scan

• Exception: Patients with lytic or blastic bone metastases as their only site of disease will be eligible for the study even though these patients are not considered to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; these patients will be evaluable for time to progression, but not response

• Patients with all other lesions, including small lesions (longest diameter < 2.0 cm with conventional techniques or < 1.0 cm with spiral CT scan) and truly non-measurable lesions including those listed below are not eligible

• Lesions that are considered non-measurable include the following:

• Bone lesions (women with bone lesions will be eligible as described above)

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast cancer

• Lymphangitis cutis/pulmonitis

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

• Cystic lesions

• Patients must have had one or two prior endocrine treatments for breast cancer in either the adjuvant or metastatic setting, exclusive of treatment-related amenorrhea or ovarian suppression; sequential use of two different third-generation aromatase inhibitors is considered "one" treatment; it is not required that tumors be resistant to such treatments; for example:

• A patient with de novo metastatic breast cancer who had never received endocrine therapy is not eligible;

• A patient who received adjuvant tamoxifen and subsequent therapy with an aromatase inhibitor (adjuvant or metastatic) is eligible;

• A patient who received an aromatase inhibitor in either the adjuvant or metastatic setting, and who discontinued therapy after several months because of side effects, is eligible;

• A patient who received an aromatase inhibitor in the adjuvant setting is eligible, regardless of whether they did or did not receive tamoxifen at some point;

• A patient who received adjuvant tamoxifen, and subsequently a nonsteroidal aromatase inhibitor and a steroidal aromatase inhibitor for advanced breast cancer in the adjuvant or metastatic setting is eligible;

• A patient who received adjuvant tamoxifen, and then a nonsteroidal aromatase inhibitor and subsequently megesterol acetate for advanced breast cancer is not eligible

• Tumors potentially sensitive to endocrine therapy, defined as >= 3 months of prior endocrine therapy without disease progression in the adjuvant or metastatic setting

• Patients must have had prior treatment in either the adjuvant or metastatic setting with a commercially available third-generation aromatase inhibitor (i.e. anastrozole, exemestane, or letrozole); it is not required that tumors be resistant to such therapies

• Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer; prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted; patients must have finished chemotherapy at least 1 week prior to starting protocol based treatment

• Patients may have received prior trastuzumab therapy for stage IV breast cancer, in combination with up to one chemotherapy and/or endocrine therapy regimen, but that must have concluded at least 3 weeks prior to starting protocol-based therapy; prior trastuzumab therapy in the adjuvant and/or neoadjuvant setting is permitted, but must have concluded at least 3 weeks prior to starting protocol-based therapy

• Prior therapy with commercially available inhibitor of EGFR (including but not limited to gefitinib, erlotinib, lapatinib or cetuximab) or experimental inhibitors of EGFR is prohibited

• Patients may have initiated bisphosphonate therapy prior to study entry; such patients will have bone lesions considered evaluable for progression but not for response

• Prior fulvestrant therapy is prohibited

• Patients receiving a gonadotropin-releasing hormone (GnRH) agonist for ovarian suppression must remain on such therapy throughout the course of protocol treatment; patients must discontinue other endocrine treatments, including systemic hormone-replacement therapy and intravaginal estrogens prior to study entry; patients must have concluded radiation therapy prior to study entry; patients must be at least 1 week from prior chemotherapy or 3 weeks from prior trastuzumab therapy, with adequate recovery of bone marrow function and performance status

• Patients must be postmenopausal women, defined as a woman fulfilling any of the following criteria:

• Age >= 60 years; or

• Age >= 45 years with an intact uterus and amenorrhea for 12 months or more; or

• History of bilateral oophorectomy; or

• Follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility; or

• Treatment with a GnRH agonist for ovarian suppression for at least 3 consecutive months prior to study registration, and remaining on such therapy throughout the course of protocol treatment

• Women who are pregnant or nursing are not eligible for the study; clinicians should advise patients that there are no data for the safety of lapatinib or fulvestrant among pregnant patients, nor data on the impact of these agents on fertility or pregnancy

• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-2

• Absence of pending visceral crisis, in the opinion of the treating physician

• Absence of acquired or inherited bleeding disorder

• Absence of need for therapeutic systemic anticoagulation (defined as maintaining international normalized ratio [INR] > 1.6); patients may take low-dose warfarin or aspirin (or equivalent) for maintenance of central venous catheter patency

• Granulocytes >= 1,000/μl

• Platelet count >= 100,000/μl

• Creatinine =< 2 mg/dl

• Total bilirubin =< 1.5 x upper limits of normal (ULN) unless due to Gilbert's syndrome

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN without liver metastases; =< 5 x ULN with liver metastases

• INR =< 1.6

• Left ventricular ejection fraction (LVEF) within institutional limits of normal

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	Arroyo Grande Community	Arroyo Grande	California	United States	93420
3	PCR Oncology	Arroyo Grande	California	United States	93420
4	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
5	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
6	Eden Hospital Medical Center	Castro Valley	California	United States	94546
7	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
8	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
9	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
10	Glendale Memorial Hospital and Health Center	Glendale	California	United States	91204
11	Saint Rose Hospital	Hayward	California	United States	94545
12	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
13	El Camino Hospital	Mountain View	California	United States	94040
14	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
15	Highland General Hospital	Oakland	California	United States	94602
16	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
17	Bay Area Tumor Institute	Oakland	California	United States	94609
18	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
19	Tom K Lee Inc	Oakland	California	United States	94609
20	Valley Care Health System - Pleasanton	Pleasanton	California	United States	94588
21	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
22	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
23	Salinas Valley Memorial	Salinas	California	United States	93901
24	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
25	Zuckerberg San Francisco General Hospital	San Francisco	California	United States	94110
26	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
27	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
28	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
29	Northbay Cancer Center	Vacaville	California	United States	95687
30	UCHealth Memorial Hospital Central	Colorado Springs	Colorado	United States	80909
31	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
32	Saint Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
33	Yale University	New Haven	Connecticut	United States	06520
34	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut	United States	06790
35	Harold Leever Regional Cancer Center	Waterbury	Connecticut	United States	06708
36	Beebe Medical Center	Lewes	Delaware	United States	19958
37	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
38	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
39	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
40	Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
41	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
42	Portneuf Medical Center	Pocatello	Idaho	United States	83201
43	Saint Anthony's Health	Alton	Illinois	United States	62002
44	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
45	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
46	Graham Hospital Association	Canton	Illinois	United States	61520
47	Memorial Hospital	Carthage	Illinois	United States	62321
48	University of Illinois	Chicago	Illinois	United States	60612
49	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
50	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
51	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
52	Eureka Hospital	Eureka	Illinois	United States	61530
53	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
54	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
55	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
56	Mason District Hospital	Havana	Illinois	United States	62644
57	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
58	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
59	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
60	Kewanee Hospital	Kewanee	Illinois	United States	61443
61	AMITA Health Adventist Medical Center	La Grange	Illinois	United States	60525
62	Mcdonough District Hospital	Macomb	Illinois	United States	61455
63	Loyola University Medical Center	Maywood	Illinois	United States	60153
64	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
65	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
66	Community Cancer Center Foundation	Normal	Illinois	United States	61761
67	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
68	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
69	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
70	Pekin Hospital	Pekin	Illinois	United States	61554
71	Proctor Hospital	Peoria	Illinois	United States	61614
72	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
73	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
74	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
75	Illinois Valley Hospital	Peru	Illinois	United States	61354
76	Valley Radiation Oncology	Peru	Illinois	United States	61354
77	Perry Memorial Hospital	Princeton	Illinois	United States	61356
78	West Suburban Medical Center	River Forest	Illinois	United States	60305
79	OSF Saint Anthony Medical Center	Rockford	Illinois	United States	61108
80	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
81	Memorial Medical Center	Springfield	Illinois	United States	62781
82	Carle Cancer Center	Urbana	Illinois	United States	61801
83	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
84	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
85	Elkhart General Hospital	Elkhart	Indiana	United States	46515
86	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
87	Goshen Center for Cancer Care	Goshen	Indiana	United States	46526
88	Community Cancer Center East	Indianapolis	Indiana	United States	46219
89	Community Cancer Center North	Indianapolis	Indiana	United States	46256
90	Community Howard Regional Health	Kokomo	Indiana	United States	46904
91	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
92	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
93	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
94	Reid Health	Richmond	Indiana	United States	47374
95	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
96	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
97	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
98	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
99	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
100	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
101	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
102	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
103	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa	United States	51503
104	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
105	Genesis Cancer Care Institute	Davenport	Iowa	United States	52804
106	Mercy Capitol	Des Moines	Iowa	United States	50307
107	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
108	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
109	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
110	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
111	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
112	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
113	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
114	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
115	Ottumwa Regional Health Center	Ottumwa	Iowa	United States	52501
116	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
117	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
118	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
119	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
120	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
121	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
122	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
123	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
124	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
125	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
126	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
127	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
128	Southwest Medical Center	Liberal	Kansas	United States	67901
129	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
130	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
131	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
132	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
133	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
134	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
135	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
136	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
137	Associates In Womens Health	Wichita	Kansas	United States	67208
138	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
139	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
140	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
141	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
142	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky	United States	40215
143	Baton Rouge General Medical Center	Baton Rouge	Louisiana	United States	70806
144	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
145	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
146	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
147	Eastern Maine Medical Center	Bangor	Maine	United States	04401
148	York Hospital	York	Maine	United States	03909
149	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
150	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
151	Saint Agnes Hospital	Baltimore	Maryland	United States	21229
152	University of Maryland Shore Medical Center at Easton	Easton	Maryland	United States	21601
153	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
154	Frederick Memorial Hospital	Frederick	Maryland	United States	21701
155	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
156	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
157	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
158	Saint Anne's Hospital	Fall River	Massachusetts	United States	02721
159	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
160	Lowell General Hospital	Lowell	Massachusetts	United States	01854
161	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
162	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
163	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
164	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
165	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
166	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
167	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
168	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
169	Holland Community Hospital	Holland	Michigan	United States	49423
170	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
171	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
172	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
173	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
174	Mid-Michigan Medical Center - Midland	Midland	Michigan	United States	48670
175	Mercy Health Partners-Hackley Campus	Muskegon	Michigan	United States	49442
176	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
177	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
178	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
179	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
180	Oncology Care Associates PLLC	Saint Joseph	Michigan	United States	49085
181	Munson Medical Center	Traverse City	Michigan	United States	49684
182	Metro Health Hospital	Wyoming	Michigan	United States	49519
183	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
184	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
185	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
186	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
187	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
188	Saint Luke's Hospital of Duluth	Duluth	Minnesota	United States	55805
189	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
190	Unity Hospital	Fridley	Minnesota	United States	55432
191	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
192	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
193	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
194	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
195	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
196	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
197	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
198	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
199	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
200	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
201	Regions Hospital	Saint Paul	Minnesota	United States	55101
202	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota	United States	55102
203	United Hospital	Saint Paul	Minnesota	United States	55102
204	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
205	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
206	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
207	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
208	Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
209	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
210	Keesler Medical Center	Keesler Air Force Base	Mississippi	United States	39534
211	Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
212	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
213	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
214	Missouri Cancer Associates	Columbia	Missouri	United States	65201
215	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
216	Freeman Health System	Joplin	Missouri	United States	64804
217	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
218	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
219	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
220	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
221	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
222	Billings Clinic Cancer Center	Billings	Montana	United States	59101
223	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
224	Saint Vincent Healthcare	Billings	Montana	United States	59101
225	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
226	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
227	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
228	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
229	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
230	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
231	Great Falls Clinic	Great Falls	Montana	United States	59405
232	Saint Peter's Community Hospital	Helena	Montana	United States	59601
233	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
234	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
235	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
236	Montana Cancer Specialists	Missoula	Montana	United States	59802
237	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
238	Community Medical Hospital	Missoula	Montana	United States	59804
239	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
240	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
241	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
242	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
243	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire	United States	03106
244	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
245	Elliot Hospital	Manchester	New Hampshire	United States	03103
246	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
247	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
248	Morristown Medical Center	Morristown	New Jersey	United States	07960
249	Virtua Memorial	Mount Holly	New Jersey	United States	08060
250	Overlook Hospital	Summit	New Jersey	United States	07902
251	Saint Francis Medical Center	Trenton	New Jersey	United States	08629
252	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
253	Virtua Voorhees	Voorhees	New Jersey	United States	08043
254	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
255	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
256	Northern Westchester Hospital	Mount Kisco	New York	United States	10549
257	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
258	Staten Island University Hospital	Staten Island	New York	United States	10305
259	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
260	Mission Hospital	Asheville	North Carolina	United States	28801
261	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
262	Duke University Medical Center	Durham	North Carolina	United States	27710
263	CaroMont Regional Medical Center	Gastonia	North Carolina	United States	28054
264	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
265	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
266	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
267	Maria Parham Hospital	Henderson	North Carolina	United States	27536
268	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
269	Southeastern Regional Medical Center	Lumberton	North Carolina	United States	28358
270	Granville Medical Center	Oxford	North Carolina	United States	27565
271	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
272	Duke Raleigh Hospital	Raleigh	North Carolina	United States	27609
273	Person Memorial Hospital	Roxboro	North Carolina	United States	27573
274	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
275	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
276	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
277	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
278	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
279	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
280	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
281	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
282	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
283	Aultman Health Foundation	Canton	Ohio	United States	44710
284	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
285	Case Western Reserve University	Cleveland	Ohio	United States	44106
286	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
287	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
288	Grant Medical Center	Columbus	Ohio	United States	43215
289	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
290	Doctors Hospital	Columbus	Ohio	United States	43228
291	Grandview Hospital	Dayton	Ohio	United States	45405
292	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
293	Miami Valley Hospital	Dayton	Ohio	United States	45409
294	Miami Valley Hospital North	Dayton	Ohio	United States	45415
295	Dayton Veterans Affairs Medical Center	Dayton	Ohio	United States	45428
296	Grady Memorial Hospital	Delaware	Ohio	United States	43015
297	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
298	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
299	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
300	Kettering Medical Center	Kettering	Ohio	United States	45429
301	Fairfield Medical Center	Lancaster	Ohio	United States	43130
302	Saint Rita's Medical Center	Lima	Ohio	United States	45801
303	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
304	Licking Memorial Hospital	Newark	Ohio	United States	43055
305	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
306	Upper Valley Medical Center	Troy	Ohio	United States	45373
307	Saint Ann's Hospital	Westerville	Ohio	United States	43081
308	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
309	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
310	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
311	Greene Memorial Hospital	Xenia	Ohio	United States	45385
312	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
313	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
314	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
315	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania	United States	19047
316	AnMed Health Hospital	Anderson	South Carolina	United States	29621
317	Saint Francis Hospital	Greenville	South Carolina	United States	29601
318	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
319	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
320	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota	United States	57401
321	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
322	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
323	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57105
324	Medical X-Ray Center	Sioux Falls	South Dakota	United States	57105
325	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
326	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
327	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
328	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38163
329	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah	United States	84003
330	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
331	Logan Regional Hospital	Logan	Utah	United States	84321
332	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
333	Intermountain Medical Center	Murray	Utah	United States	84107
334	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
335	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
336	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
337	Intermountain Health Care	Salt Lake City	Utah	United States	84103
338	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
339	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
340	LDS Hospital	Salt Lake City	Utah	United States	84143
341	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
342	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
343	Danville Regional Medical Center	Danville	Virginia	United States	24541
344	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
345	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
346	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
347	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
348	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
349	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
350	Minor and James Medical PLLC	Seattle	Washington	United States	98104
351	Kaiser Permanente Washington	Seattle	Washington	United States	98112
352	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
353	University of Washington Medical Center	Seattle	Washington	United States	98195
354	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
355	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
356	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
357	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
358	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
359	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
360	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
361	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin	United States	53548
362	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
363	Dean Hematology and Oncology Clinic	Madison	Wisconsin	United States	53717
364	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
365	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
366	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
367	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
368	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Harold J Burstein, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00390455
• Other Study ID Numbers: NCI-2009-00475; NCI-2009-00475; CDR0000510452; CALGB-40302; CALGB-40302; U10CA180821; U10CA031946
• First Posted: Oct 19, 2006
• Last Update Posted: Dec 20, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Fulvestrant; Lapatinib

Study Results

Participant Flow

Recruitment Details	Between September 2006 and July 2010, 295 participants were recruited.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Period Title: Overall Study
STARTED	148	147
COMPLETED	116	124
NOT COMPLETED	32	23

Baseline Characteristics

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)	Total
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.	Total of all reporting groups
Overall Participants	146	145	291
Age, Customized (participants) [Number]
<40	8 5.5%	7 4.8%	15 5.2%
40-49	21 14.4%	17 11.7%	38 13.1%
50-59	49 33.6%	54 37.2%	103 35.4%
60-69	41 28.1%	47 32.4%	88 30.2%
70+	27 18.5%	20 13.8%	47 16.2%
Sex: Female, Male (Count of Participants)
Female	146 100%	145 100%	291 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 4.8%	7 4.8%	14 4.8%
Not Hispanic or Latino	130 89%	129 89%	259 89%
Unknown or Not Reported	9 6.2%	9 6.2%	18 6.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.3%
Asian	4 2.7%	2 1.4%	6 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 7.5%	8 5.5%	19 6.5%
White	127 87%	132 91%	259 89%
More than one race	0 0%	2 1.4%	2 0.7%
Unknown or Not Reported	3 2.1%	1 0.7%	4 1.4%
Region of Enrollment (participants) [Number]
United States	146 100%	145 100%	291 100%
Prior tamoxifen therapy (participants) [Number]
Yes	83 56.8%	82 56.6%	165 56.7%
No	63 43.2%	63 43.4%	126 43.3%
Bond disease only (participants) [Number]
Yes	45 30.8%	43 29.7%	88 30.2%
No	101 69.2%	102 70.3%	203 69.8%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria).
Time Frame	Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

4 participants who never received protocol therapy were excluded.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	146	145
Median (95% Confidence Interval) [months]	4.7	3.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Lapatinib), Arm II (Placebo)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The null hypothesis then is that the hazard ratio of the two treatment arms is 1.0; the alternative hypothesis is that the hazard ratio of the control to the experimental regimen is 1.5 (0.67). The test of these hypotheses is one-sided (alpha = 0.025), and interim analyses will be used to stop for futility and superiority. Under these assumptions, there is at least 90% power to detect the stated difference in median PFS between the two treatment arms.
Statistical Test of Hypothesis	p-Value	0.37
	Comments	Tests were stratified by prior tamoxifen therapy (yes/no) and bone disease only (yes/no).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Tumor Response Rate
Description	Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who started protocol therapy and had measurable disease were evaluated.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	101	103
Number (95% Confidence Interval) [percentage of participants]	20 13.7%	9 6.2%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was measured as the interval from study entry until death, from any cause, or last contact.
Time Frame	Study entry to death or last follow-up, up to 5 years

Outcome Measure Data

Analysis Population Description

4 participants who never started protocol therapy were excluded.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	146	145
Median (95% Confidence Interval) [months]	29.9	26.4

4. Other Pre-specified Outcome

Title	Progression-free Survival for Participants With HER2-negative Tumors
Description	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who began protocol therapy with HER-2 negative tumors were analyzed.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	122	113
Median (95% Confidence Interval) [months]	4.1	3.8

5. Other Pre-specified Outcome

Title	Progression-free Survival for Participants With HER2-positive Tumors
Description	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, whichever occurred first.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who started protocol therapy and had HER2-positive disease were analyzed.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	24	30
Median (95% Confidence Interval) [months]	5.9	3.3

6. Other Pre-specified Outcome

Title	Objective Tumor Response Rate for Participants With HER2-negative Tumors
Description	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who started protocol therapy, had measurable disease and HER-2 negative disease were analyzed.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	32	32
Number (95% Confidence Interval) [percentage of participants]	13 8.9%	23 15.9%

7. Other Pre-specified Outcome

Title	Objective Tumor Response Rate for Participants With HER2-positive Tumors
Description	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who started protocol therapy, had measurable disease and HER-2 positive disease were analyzed.

Arm/Group Title	Arm I (Lapatinib)	Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.	Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
Measure Participants	8	13
Number (95% Confidence Interval) [percentage of participants]	38 26%	17 11.7%

Adverse Events

Adverse Event Reporting Description	Adverse event was available on 278 participants (Arm I: 141, Arm II: 137)
Arm/Group Title	Arm I (Lapatinib)		Arm II (Placebo)
Arm/Group Description	Patients receive 1500 mg lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg)of each subsequent course.		Patients receive placebo PO QD on days 1-28 and fulvestrant IM on days 1 (500 mg) and 15 (250 mg) of course 1 and on day 1 (250 mg) of each subsequent course.
All Cause Mortality
	Arm I (Lapatinib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Lapatinib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/141 (8.5%)		14/137 (10.2%)
Cardiac disorders
Cardiac pain	1/141 (0.7%)	1	1/137 (0.7%)	1
Gastrointestinal disorders
Constipation	1/141 (0.7%)	1	2/137 (1.5%)	2
Diarrhea	7/141 (5%)	7	4/137 (2.9%)	4
Gastrointestinal disorder	0/141 (0%)	0	1/137 (0.7%)	1
Nausea	5/141 (3.5%)	5	3/137 (2.2%)	3
Vomiting	2/141 (1.4%)	2	1/137 (0.7%)	1
General disorders
Chest pain	1/141 (0.7%)	2	1/137 (0.7%)	1
Disease progression	1/141 (0.7%)	1	0/137 (0%)	0
Fatigue	8/141 (5.7%)	8	5/137 (3.6%)	5
Gait abnormal	0/141 (0%)	0	1/137 (0.7%)	1
Injection site reaction	1/141 (0.7%)	1	0/137 (0%)	0
Pain	1/141 (0.7%)	1	2/137 (1.5%)	2
Infections and infestations
Sepsis	0/141 (0%)	0	1/137 (0.7%)	1
Urinary tract infection	3/141 (2.1%)	3	2/137 (1.5%)	2
Injury, poisoning and procedural complications
Fracture	0/141 (0%)	0	1/137 (0.7%)	1
Investigations
Alanine aminotransferase increased	0/141 (0%)	0	1/137 (0.7%)	2
Alkaline phosphatase increased	1/141 (0.7%)	1	0/137 (0%)	0
Aspartate aminotransferase increased	0/141 (0%)	0	1/137 (0.7%)	2
Blood bilirubin increased	1/141 (0.7%)	1	0/137 (0%)	0
Metabolism and nutrition disorders
Anorexia	4/141 (2.8%)	4	1/137 (0.7%)	1
Blood glucose increased	0/141 (0%)	0	1/137 (0.7%)	1
Dehydration	1/141 (0.7%)	1	0/137 (0%)	0
Serum sodium decreased	1/141 (0.7%)	1	1/137 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/141 (0%)	0	1/137 (0.7%)	1
Bone pain	0/141 (0%)	0	1/137 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare	0/141 (0%)	0	1/137 (0.7%)	1
Nervous system disorders
Dizziness	1/141 (0.7%)	1	0/137 (0%)	0
Headache	2/141 (1.4%)	2	0/137 (0%)	0
Ischemia cerebrovascular	0/141 (0%)	0	1/137 (0.7%)	1
Peripheral motor neuropathy	0/141 (0%)	0	1/137 (0.7%)	1
Psychiatric disorders
Insomnia	0/141 (0%)	0	1/137 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/141 (2.1%)	4	2/137 (1.5%)	2
Pneumonitis	2/141 (1.4%)	2	0/137 (0%)	0
Skin and subcutaneous tissue disorders
Rash acneiform	4/141 (2.8%)	5	0/137 (0%)	0
Rash desquamating	2/141 (1.4%)	2	1/137 (0.7%)	1
Skin ulceration	1/141 (0.7%)	1	0/137 (0%)	0
Vascular disorders
Hot flashes	2/141 (1.4%)	2	3/137 (2.2%)	4
Thrombosis	2/141 (1.4%)	2	1/137 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Lapatinib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/141 (90.8%)		114/137 (83.2%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/141 (3.5%)	5	5/137 (3.6%)	12
Cardiac disorders
Left ventricular failure	3/141 (2.1%)	6	3/137 (2.2%)	3
Eye disorders
Diplopia	0/141 (0%)	0	1/137 (0.7%)	1
Eye pain	1/141 (0.7%)	1	0/137 (0%)	0
Vision blurred	0/141 (0%)	0	1/137 (0.7%)	2
Gastrointestinal disorders
Abdominal pain	1/141 (0.7%)	2	0/137 (0%)	0
Ascites	1/141 (0.7%)	1	0/137 (0%)	0
Constipation	20/141 (14.2%)	25	25/137 (18.2%)	29
Diarrhea	88/141 (62.4%)	206	30/137 (21.9%)	54
Dyspepsia	2/141 (1.4%)	2	2/137 (1.5%)	2
Flatulence	0/141 (0%)	0	1/137 (0.7%)	1
Gastrointestinal disorder	1/141 (0.7%)	1	0/137 (0%)	0
Mucositis oral	1/141 (0.7%)	1	0/137 (0%)	0
Nausea	49/141 (34.8%)	76	41/137 (29.9%)	51
Vomiting	22/141 (15.6%)	26	9/137 (6.6%)	12
General disorders
Chest pain	1/141 (0.7%)	1	1/137 (0.7%)	1
Edema limbs	0/141 (0%)	0	1/137 (0.7%)	1
Fatigue	78/141 (55.3%)	205	73/137 (53.3%)	145
Gait abnormal	0/141 (0%)	0	1/137 (0.7%)	3
Ill-defined disorder	1/141 (0.7%)	1	0/137 (0%)	0
Injection site reaction	4/141 (2.8%)	7	10/137 (7.3%)	17
Pain	1/141 (0.7%)	2	1/137 (0.7%)	1
Infections and infestations
Bronchitis	1/141 (0.7%)	1	0/137 (0%)	0
Nail infection	1/141 (0.7%)	1	0/137 (0%)	0
Upper respiratory infection	0/141 (0%)	0	1/137 (0.7%)	1
Urinary tract infection	5/141 (3.5%)	6	4/137 (2.9%)	5
Investigations
Activated partial thromboplastin time prolonged	0/141 (0%)	0	1/137 (0.7%)	1
Alanine aminotransferase increased	4/141 (2.8%)	6	0/137 (0%)	0
Alkaline phosphatase increased	3/141 (2.1%)	4	0/137 (0%)	0
Aspartate aminotransferase increased	8/141 (5.7%)	10	2/137 (1.5%)	2
Blood bilirubin increased	1/141 (0.7%)	1	0/137 (0%)	0
Creatinine increased	2/141 (1.4%)	2	2/137 (1.5%)	2
Leukocyte count decreased	1/141 (0.7%)	1	0/137 (0%)	0
Weight loss	2/141 (1.4%)	4	1/137 (0.7%)	2
Metabolism and nutrition disorders
Anorexia	19/141 (13.5%)	27	21/137 (15.3%)	25
Blood glucose increased	4/141 (2.8%)	6	0/137 (0%)	0
Serum potassium decreased	2/141 (1.4%)	4	0/137 (0%)	0
Serum potassium increased	1/141 (0.7%)	1	0/137 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	3/141 (2.1%)	3	6/137 (4.4%)	15
Back pain	5/141 (3.5%)	9	1/137 (0.7%)	3
Bone pain	3/141 (2.1%)	3	2/137 (1.5%)	2
Chest wall pain	0/141 (0%)	0	1/137 (0.7%)	2
Developmental disturbance	1/141 (0.7%)	2	0/137 (0%)	0
Muscle weakness lower limb	0/141 (0%)	0	1/137 (0.7%)	1
Myalgia	0/141 (0%)	0	1/137 (0.7%)	1
Neck pain	1/141 (0.7%)	2	2/137 (1.5%)	5
Osteoporosis	0/141 (0%)	0	1/137 (0.7%)	1
Pain in extremity	1/141 (0.7%)	2	4/137 (2.9%)	4
Nervous system disorders
Dizziness	0/141 (0%)	0	1/137 (0.7%)	1
Headache	19/141 (13.5%)	24	16/137 (11.7%)	19
Peripheral sensory neuropathy	2/141 (1.4%)	2	2/137 (1.5%)	2
Psychiatric disorders
Anxiety	1/141 (0.7%)	1	0/137 (0%)	0
Depression	2/141 (1.4%)	2	0/137 (0%)	0
Insomnia	1/141 (0.7%)	4	1/137 (0.7%)	1
Renal and urinary disorders
Cystitis	0/141 (0%)	0	1/137 (0.7%)	1
Ureteric obstruction	1/141 (0.7%)	1	0/137 (0%)	0
Urinary frequency	0/141 (0%)	0	1/137 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/141 (1.4%)	2	3/137 (2.2%)	3
Dyspnea	5/141 (3.5%)	5	4/137 (2.9%)	6
Dyspnea (shortness of breath)	1/141 (0.7%)	1	1/137 (0.7%)	1
Hypoxia	1/141 (0.7%)	1	0/137 (0%)	0
Pleural effusion	0/141 (0%)	0	1/137 (0.7%)	1
Pneumonitis	2/141 (1.4%)	2	0/137 (0%)	0
Respiratory disorder	1/141 (0.7%)	1	0/137 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/141 (1.4%)	3	1/137 (0.7%)	2
Dry skin	2/141 (1.4%)	11	1/137 (0.7%)	4
Nail disorder	1/141 (0.7%)	3	0/137 (0%)	0
Pain of skin	1/141 (0.7%)	1	0/137 (0%)	0
Pruritus	2/141 (1.4%)	2	1/137 (0.7%)	1
Rash acneiform	58/141 (41.1%)	160	6/137 (4.4%)	16
Rash desquamating	16/141 (11.3%)	23	11/137 (8%)	13
Skin disorder	1/141 (0.7%)	2	0/137 (0%)	0
Sweating	1/141 (0.7%)	1	0/137 (0%)	0
Vascular disorders
Hot flashes	38/141 (27%)	78	50/137 (36.5%)	104
Hypertension	1/141 (0.7%)	1	0/137 (0%)	0
Thrombosis	1/141 (0.7%)	1	0/137 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.