Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00770809
• Collaborator: (none)
• Enrollment: 305
• Locations: 318
• Arms: 3
• Patients Per Site: 1

Study Details

Study Description

Brief Summary

This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Male Breast Carcinoma; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7	Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Drug: Paclitaxel; Biological: Trastuzumab	Phase 3

Detailed Description

PRIMARY OBJECTIVE:

1. To determine if the pathologic complete response (pCR) in the breast to neoadjuvant weekly paclitaxel with trastuzumab plus lapatinib (THL) is 20% greater than the pCR to weekly paclitaxel with trastuzumab alone (TH).

SECONDARY OBJECTIVES:

1. To determine the pathologic complete response in the breast and axilla, using American Joint Committee on Cancer (AJCC) Tumor, Lymph Nodes and Metastasis (TMN) criteria (version 6), to neoadjuvant weekly paclitaxel plus human epidermal growth factor 2 (HER2)- targeted therapy in patients with HER2-positive operable breast cancer.

2. To evaluate residual cancer burden (RCB) as a predictor of long term relapse free survival (RFS) and overall survival (OS).

3. To document the toxicity of all chemotherapeutic regimens (THL, TH). IV. To determine the correlation between clinical, radiographic and pathologic response.

4. To compare overall survival (OS), relapse free survival (RFS) and time to first failure (TFF) among the treatment groups.

5. To obtain blood, fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood, serum and tissue that are likely to influence response to and toxicity of trastuzumab alone or trastuzumab plus lapatinib, when given with paclitaxel.

6. To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.

7. To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy.

8. To evaluate pharmacogenomic determinants of toxicity.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate orally (PO) once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive trastuzumab and paclitaxel as in arm I.

ARM III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11) Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy).

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial of Paclitaxel +Trastuzumab + Lapatinib Versus Paclitaxel + Trastuzumab as Neoadjuvant Treatment of HER2-Positive Primary Breast Cancer
• Actual Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jan 31, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (THL) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb ; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Biological: Trastuzumab; Given IV; Other Names: ABP 980 ALT02 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 Herzuma Kanjinti MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 Ogivri Ontruzant PF-05280014 rhuMAb HER2 RO0452317 SB3 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar ALT02 trastuzumab biosimilar EG12014 Trastuzumab Biosimilar HLX02 Trastuzumab Biosimilar PF-05280014 Trastuzumab Biosimilar SB3 Trastuzumab Biosimilar SIBP-01 Trastuzumab-anns Trastuzumab-dkst Trastuzumab-dttb Trastuzumab-pkrb Trastuzumab-qyyp Trazimera
Active Comparator: Arm II (TH) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Biological: Trastuzumab; Given IV; Other Names: ABP 980 ALT02 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 Herzuma Kanjinti MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 Ogivri Ontruzant PF-05280014 rhuMAb HER2 RO0452317 SB3 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar ALT02 trastuzumab biosimilar EG12014 Trastuzumab Biosimilar HLX02 Trastuzumab Biosimilar PF-05280014 Trastuzumab Biosimilar SB3 Trastuzumab Biosimilar SIBP-01 Trastuzumab-anns Trastuzumab-dkst Trastuzumab-dttb Trastuzumab-pkrb Trastuzumab-qyyp Trazimera
Experimental: Arm III (TL) Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)	Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb ; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

Outcome Measures

Primary Outcome Measures

1. pCR Rate [At time of surgery]

   Complete pathological response is defined as the absence of residual invasive carcinoma in the breast at the time of definitive surgical removal. Pathologic complete response in the lymph nodes is defined as no detectable invasive tumor by H&E. Analysis will use a chi-square test for the difference in proportions of patients on the THL arm versus the TH arm who achieve a pCR. Exact binomial methods will be used to construct 95% confidence intervals around the pCR incidence for each arm.

Secondary Outcome Measures

1. Pathologic Stage in the Breast and Axilla [At time of surgery]

   Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor, lymph nodes, metastasis) staging system.

2. Radiographic Response Rate (at Completion of Neoadjuvant Therapy) [Week 16]

   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).

3. Overall Survival [Time from randomization to death or last follow-up (up to 10 years)]

   Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method

4. Relapse-free Survival (RFS) [Time from surgery to any recurrence (up to 10 years)]

   Relapse free survival is defined as the interval from definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Patients who do not undergo definitive surgery will not be assessable for RFS. Distribution was estimated using the Kaplan Meier product-limit method.

5. Time to First Failure [Time from study entry to any recurrence ( up to 10 years)]

   Time to first failure is defined as the interval from study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Distribution was estimated using the Kaplan Meier product-limit method.

6. Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3 [Up to 30 days post-treatment]

   The type and grade of treatment-related toxicity will be tabulated by treatment arm.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologic confirmation of invasive breast cancer; patients with inflammatory breast cancer are not eligible

• Clinical stage II-III operable invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy

• Patients with multicentric or bilateral disease are eligible as long as the target lesion meets the eligibility criteria for this study

• Staging to rule out metastatic disease is recommended for clinical stage III patients

• Tumors must be HER2 positive defined as HER2 3+ by immunohistochemical (IHC) assays or gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2 on invasive tumor

• Estrogen receptor (ER) and progesterone receptor (PgR) status must be known

• The target lesion in the breast must be >= 1 cm on physical examination or by radiographic measurement; palpable axillary adenopathy will be documented but not serve as measurable disease for the primary endpoint; patients with axillary disease only are not eligible to participate

• Patient agrees to provide pretreatment biopsies

• No prior chemotherapy, hormone therapy, biologic, or radiation therapy with therapeutic intent for this cancer

• Cardiac ejection fraction must be >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan

• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1

• Patients must not be pregnant or nursing

• Absolute neutrophil count (ANC) >= 1,000/ul

• Platelet count >= 100,000/ul

• Bilirubin =< 1.5 times upper limit of normal

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN)

• Serum beta-human chorionic gonadotropin (HCG) negative (in female patients unless status-post (s/p) hysterectomy or menopausal or no menses for 24 consecutive months); assay must have a sensitivity of at least 50 mIU/mL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
2	Sparks Regional Medical Center	Fort Smith	Arkansas	United States	72901
3	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
4	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
5	Eden Hospital Medical Center	Castro Valley	California	United States	94546
6	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
7	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
8	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
9	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
10	El Camino Hospital	Mountain View	California	United States	94040
11	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
12	Highland General Hospital	Oakland	California	United States	94602
13	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
14	Bay Area Tumor Institute	Oakland	California	United States	94609
15	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
16	Tom K Lee Inc	Oakland	California	United States	94609
17	Desert Regional Medical Center	Palm Springs	California	United States	92262
18	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
19	Valley Care Health System - Pleasanton	Pleasanton	California	United States	94588
20	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
21	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
22	Saint Helena Hospital	Saint Helena	California	United States	94574
23	Salinas Valley Memorial	Salinas	California	United States	93901
24	Zuckerberg San Francisco General Hospital	San Francisco	California	United States	94110
25	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
26	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
27	The Medical Center of Aurora	Aurora	Colorado	United States	80012
28	Boulder Community Hospital	Boulder	Colorado	United States	80301
29	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
30	Porter Adventist Hospital	Denver	Colorado	United States	80210
31	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
32	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
33	Rose Medical Center	Denver	Colorado	United States	80220
34	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
35	Swedish Medical Center	Englewood	Colorado	United States	80113
36	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
37	North Colorado Medical Center	Greeley	Colorado	United States	80631
38	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
39	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
40	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
41	Longmont United Hospital	Longmont	Colorado	United States	80501
42	McKee Medical Center	Loveland	Colorado	United States	80539
43	Parker Adventist Hospital	Parker	Colorado	United States	80138
44	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
45	North Suburban Medical Center	Thornton	Colorado	United States	80229
46	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
47	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
48	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
49	Middlesex Hospital	Middletown	Connecticut	United States	06457
50	Beebe Medical Center	Lewes	Delaware	United States	19958
51	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
52	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
53	Halifax Health Medical Center-Centers for Oncology	Daytona Beach	Florida	United States	32114
54	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
55	Florida Cancer Specialists-Gainesville Cancer Center	Gainesville	Florida	United States	32605
56	Jupiter Medical Center	Jupiter	Florida	United States	33458
57	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
58	Cleveland Clinic-Weston	Weston	Florida	United States	33331
59	Piedmont Hospital	Atlanta	Georgia	United States	30309
60	Atlanta Regional CCOP	Atlanta	Georgia	United States	30342
61	Emory Saint Joseph's Hospital	Atlanta	Georgia	United States	30342
62	Northside Hospital	Atlanta	Georgia	United States	30342
63	WellStar Cobb Hospital	Austell	Georgia	United States	30106
64	John B Amos Cancer Center	Columbus	Georgia	United States	31904
65	Dekalb Medical Center	Decatur	Georgia	United States	30033
66	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
67	Northside Hospital - Gwinnett	Lawrenceville	Georgia	United States	30046
68	Medical Center of Central Georgia	Macon	Georgia	United States	31201
69	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
70	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
71	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
72	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
73	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
74	Saint Anthony's Health	Alton	Illinois	United States	62002
75	Mount Sinai Hospital Medical Center	Chicago	Illinois	United States	60608
76	University of Illinois	Chicago	Illinois	United States	60612
77	Presence Resurrection Medical Center	Chicago	Illinois	United States	60631
78	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
79	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
80	Advocate Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
81	Duly Health and Care Joliet	Joliet	Illinois	United States	60435
82	Loyola University Medical Center	Maywood	Illinois	United States	60153
83	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
84	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
85	Swedish American Hospital	Rockford	Illinois	United States	61104
86	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
87	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
88	Reid Health	Richmond	Indiana	United States	47374
89	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
90	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
91	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
92	Mercy Capitol	Des Moines	Iowa	United States	50307
93	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
94	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
95	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
96	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
97	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
98	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
99	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
100	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
101	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
102	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
103	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
104	Hutchinson Regional Medical Center	Hutchinson	Kansas	United States	67502
105	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
106	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
107	Salina Regional Health Center	Salina	Kansas	United States	67401
108	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
109	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
110	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
111	Eastern Maine Medical Center	Bangor	Maine	United States	04401
112	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
113	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
114	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
115	TidalHealth Peninsula Regional	Salisbury	Maryland	United States	21801
116	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
117	Sturdy Memorial Hospital	Attleboro	Massachusetts	United States	02703
118	Tufts Medical Center	Boston	Massachusetts	United States	02111
119	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
120	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
121	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
122	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
123	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135
124	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts	United States	01757
125	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
126	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
127	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
128	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
129	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
130	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
131	Hurley Medical Center	Flint	Michigan	United States	48503
132	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
133	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
134	Allegiance Health	Jackson	Michigan	United States	49201
135	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
136	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
137	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
138	Sparrow Hospital	Lansing	Michigan	United States	48912
139	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
140	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
141	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
142	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
143	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
144	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
145	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota	United States	56001
146	Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
147	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
148	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
149	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
150	Truman Medical Centers	Kansas City	Missouri	United States	64108
151	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
152	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
153	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
154	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
155	Comprehensive Cancer Care PC	Saint Louis	Missouri	United States	63141
156	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
157	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
158	Billings Clinic Cancer Center	Billings	Montana	United States	59101
159	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
160	Saint Vincent Healthcare	Billings	Montana	United States	59101
161	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
162	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
163	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
164	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
165	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
166	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
167	Great Falls Clinic	Great Falls	Montana	United States	59405
168	Northern Montana Hospital	Havre	Montana	United States	59501
169	Saint Peter's Community Hospital	Helena	Montana	United States	59601
170	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
171	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
172	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
173	Montana Cancer Specialists	Missoula	Montana	United States	59802
174	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
175	Community Medical Hospital	Missoula	Montana	United States	59804
176	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
177	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
178	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
179	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
180	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
181	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
182	Creighton University Medical Center	Omaha	Nebraska	United States	68131
183	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
184	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
185	Renown Regional Medical Center	Reno	Nevada	United States	89502
186	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
187	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire	United States	03431
188	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
189	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
190	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire	United States	03102
191	Elliot Hospital	Manchester	New Hampshire	United States	03103
192	Solinsky Center for Cancer Care	Manchester	New Hampshire	United States	03103
193	Foundation Medical Partners	Nashua	New Hampshire	United States	03060
194	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
195	Morristown Medical Center	Morristown	New Jersey	United States	07960
196	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07101
197	Overlook Hospital	Summit	New Jersey	United States	07902
198	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico	United States	87102
199	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
200	Hematology Oncology Associates	Albuquerque	New Mexico	United States	87106
201	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
202	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
203	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
204	Queens Hospital Center	Jamaica	New York	United States	11432
205	Northwell Health NCORP	Lake Success	New York	United States	11042
206	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
207	North Shore University Hospital	Manhasset	New York	United States	11030
208	Garnet Health Medical Center	Middletown	New York	United States	10940
209	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
210	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
211	Vassar Brothers Medical Center	Poughkeepsie	New York	United States	12601
212	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
213	Mission Hospital	Asheville	North Carolina	United States	28801
214	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
215	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
216	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina	United States	28025
217	Duke University Medical Center	Durham	North Carolina	United States	27710
218	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
219	East Carolina University	Greenville	North Carolina	United States	27834
220	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
221	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
222	UNC Rex Cancer Center	Raleigh	North Carolina	United States	27607
223	Marion L Shepard Cancer Center at Vidant Beaufort Hospital	Washington	North Carolina	United States	27889
224	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
225	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
226	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
227	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
228	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
229	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio	United States	44122
230	Aultman Health Foundation	Canton	Ohio	United States	44710
231	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
232	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
233	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
234	Grandview Hospital	Dayton	Ohio	United States	45405
235	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
236	Miami Valley Hospital	Dayton	Ohio	United States	45409
237	Miami Valley Hospital North	Dayton	Ohio	United States	45415
238	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
239	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
240	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
241	Wayne Hospital	Greenville	Ohio	United States	45331
242	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
243	Kettering Medical Center	Kettering	Ohio	United States	45429
244	Saint Rita's Medical Center	Lima	Ohio	United States	45801
245	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
246	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
247	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
248	Upper Valley Medical Center	Troy	Ohio	United States	45373
249	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
250	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
251	Greene Memorial Hospital	Xenia	Ohio	United States	45385
252	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
253	Cancer Care Associates	Oklahoma City	Oklahoma	United States	73120
254	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania	United States	16505
255	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
256	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
257	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
258	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
259	Kent Hospital	Warwick	Rhode Island	United States	02886
260	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
261	Roper Hospital	Charleston	South Carolina	United States	29401
262	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
263	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
264	Saint Francis Hospital	Greenville	South Carolina	United States	29601
265	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
266	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
267	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
268	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
269	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
270	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
271	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
272	Lexington Medical Center	West Columbia	South Carolina	United States	29169
273	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
274	Nashville Oncology Associates PC	Nashville	Tennessee	United States	37203
275	Meharry Medical College	Nashville	Tennessee	United States	37208
276	Doctor's Hospital of Laredo	Laredo	Texas	United States	78041
277	Texas Tech University Health Sciences Center-Lubbock	Lubbock	Texas	United States	79430
278	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
279	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
280	Danville Regional Medical Center	Danville	Virginia	United States	24541
281	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia	United States	22408
282	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia	United States	24501
283	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
284	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
285	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
286	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
287	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
288	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
289	Saint Francis Hospital	Federal Way	Washington	United States	98003
290	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
291	EvergreenHealth Medical Center	Kirkland	Washington	United States	98033
292	Saint Clare Hospital	Lakewood	Washington	United States	98499
293	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
294	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
295	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
296	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
297	Virginia Mason Medical Center	Seattle	Washington	United States	98101
298	Minor and James Medical PLLC	Seattle	Washington	United States	98104
299	Pacific Medical Center-First Hill	Seattle	Washington	United States	98104
300	Kaiser Permanente Washington	Seattle	Washington	United States	98112
301	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
302	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
303	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
304	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
305	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
306	Providence Holy Family Hospital	Spokane	Washington	United States	99208
307	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
308	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
309	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
310	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
311	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
312	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
313	Saint Mary's Medical Center	Huntington	West Virginia	United States	25702
314	Camden Clark Medical Center	Parkersburg	West Virginia	United States	26101
315	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
316	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin	United States	53210
317	Welch Cancer Center	Sheridan	Wyoming	United States	82801
318	San Juan City Hospital	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lisa A Carey, 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: NCT00770809
• Other Study ID Numbers: NCI-2009-01073; NCI-2009-01073; CDR0000616648; CALGB 40601; CALGB-40601; U10CA180821; U10CA031946
• First Posted: Oct 10, 2008
• Last Update Posted: Mar 2, 2022
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel; Lapatinib; Trastuzumab biosimilar HLX02; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Arm I (THL)	Arm II (TH)	Arm III (TL)
Arm/Group Description	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
Period Title: Overall Study
STARTED	118	120	67
COMPLETED	101	110	44
NOT COMPLETED	17	10	23

Baseline Characteristics

Arm/Group Title	Arm I (THL)	Arm II (TH)	Arm III (TL)	Total
Arm/Group Description	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)	Total of all reporting groups
Overall Participants	118	120	67	305
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48.5	50.3	48.3	49.4
Sex: Female, Male (Count of Participants)
Female	117 99.2%	119 99.2%	67 100%	303 99.3%
Male	1 0.8%	1 0.8%	0 0%	2 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	1 0.8%	0 0%	2 0.7%
Asian	4 3.4%	8 6.7%	5 7.5%	17 5.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.8%	0 0%	1 0.3%
Black or African American	12 10.2%	8 6.7%	7 10.4%	27 8.9%
White	95 80.5%	97 80.8%	51 76.1%	243 79.7%
More than one race	2 1.7%	0 0%	0 0%	2 0.7%
Unknown or Not Reported	4 3.4%	5 4.2%	4 6%	13 4.3%
Region of Enrollment (participants) [Number]
United States	118 100%	120 100%	67 100%	305 100%
Clinical Stage (participants) [Number]
Stage II	81 68.6%	80 66.7%	48 71.6%	209 68.5%
Stage III	37 31.4%	40 33.3%	19 28.4%	96 31.5%
Hormone Receptor Status (participants) [Number]
ER/PgR Positive	70 59.3%	70 58.3%	39 58.2%	179 58.7%
ER/PgR or Negative	48 40.7%	50 41.7%	28 41.8%	126 41.3%

Outcome Measures

1. Primary Outcome

Title	pCR Rate
Description	Complete pathological response is defined as the absence of residual invasive carcinoma in the breast at the time of definitive surgical removal. Pathologic complete response in the lymph nodes is defined as no detectable invasive tumor by H&E. Analysis will use a chi-square test for the difference in proportions of patients on the THL arm versus the TH arm who achieve a pCR. Exact binomial methods will be used to construct 95% confidence intervals around the pCR incidence for each arm.
Time Frame	At time of surgery

Outcome Measure Data

Analysis Population Description

Participants who did not start protocol therapy or withdrew prior to surgery are excluded. Participants who did not undergo surgery are considered no having a pCR.

Arm/Group Title	Arm I (THL)	Arm II (TH)	Arm III (TL)
Arm/Group Description	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
Measure Participants	116	117	63
Number (95% Confidence Interval) [percentage of participants]	56 47.5%	46 38.3%	32 47.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (THL), Arm II (TH)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Participants were stratified by clinical stage (II vs III) and hormone receptor status (positive/negative).
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (TH), Arm III (TL)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments	Participants were stratified by clinical stage (II vs III) and hormone receptor status (positive/negative).
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Pathologic Stage in the Breast and Axilla
Description	Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor, lymph nodes, metastasis) staging system.
Time Frame	At time of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Radiographic Response Rate (at Completion of Neoadjuvant Therapy)
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).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method
Time Frame	Time from randomization to death or last follow-up (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Relapse-free Survival (RFS)
Description	Relapse free survival is defined as the interval from definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Patients who do not undergo definitive surgery will not be assessable for RFS. Distribution was estimated using the Kaplan Meier product-limit method.
Time Frame	Time from surgery to any recurrence (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Time to First Failure
Description	Time to first failure is defined as the interval from study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Distribution was estimated using the Kaplan Meier product-limit method.
Time Frame	Time from study entry to any recurrence ( up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3
Description	The type and grade of treatment-related toxicity will be tabulated by treatment arm.
Time Frame	Up to 30 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Arm/Group Title	Arm I (THL)		Arm II (TH)		Arm III (TL)
Arm/Group Description	Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.		Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.		Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
All Cause Mortality
	Arm I (THL)		Arm II (TH)		Arm III (TL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (THL)		Arm II (TH)		Arm III (TL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/115 (13%)		12/115 (10.4%)		6/65 (9.2%)
Blood and lymphatic system disorders
Febrile neutropenia	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Hemoglobin decreased	9/115 (7.8%)	11	7/115 (6.1%)	8	4/65 (6.2%)	5
Cardiac disorders
Cardiopulmonary arrest	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Pericarditis	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Gastrointestinal disorders
Abdominal pain	1/115 (0.9%)	1	1/115 (0.9%)	1	0/65 (0%)	0
Constipation	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Diarrhea	12/115 (10.4%)	16	5/115 (4.3%)	5	5/65 (7.7%)	6
Nausea	7/115 (6.1%)	9	2/115 (1.7%)	3	2/65 (3.1%)	2
Pancreatitis	1/115 (0.9%)	1	0/115 (0%)	0	1/65 (1.5%)	1
Vomiting	3/115 (2.6%)	3	1/115 (0.9%)	1	1/65 (1.5%)	1
General disorders
Edema limbs	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Fatigue	11/115 (9.6%)	15	8/115 (7%)	9	4/65 (6.2%)	4
Immune system disorders
Hypersensitivity	1/115 (0.9%)	1	1/115 (0.9%)	1	0/65 (0%)	0
Infections and infestations
Gallbladder infection	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Infection	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Pneumonia	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Sepsis	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Skin infection	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Soft tissue infection	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Urinary tract infection	2/115 (1.7%)	4	0/115 (0%)	0	0/65 (0%)	0
Injury, poisoning and procedural complications
Seroma	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Investigations
Alanine aminotransferase increased	1/115 (0.9%)	2	2/115 (1.7%)	2	3/65 (4.6%)	3
Amylase increased	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Aspartate aminotransferase increased	2/115 (1.7%)	3	1/115 (0.9%)	1	2/65 (3.1%)	2
Leukocyte count decreased	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Lipase increased	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Neutrophil count decreased	5/115 (4.3%)	6	3/115 (2.6%)	4	2/65 (3.1%)	2
Metabolism and nutrition disorders
Dehydration	0/115 (0%)	0	1/115 (0.9%)	1	1/65 (1.5%)	1
Serum potassium decreased	3/115 (2.6%)	3	0/115 (0%)	0	1/65 (1.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Bone pain	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Chest wall pain	1/115 (0.9%)	2	0/115 (0%)	0	1/65 (1.5%)	1
Myalgia	3/115 (2.6%)	3	2/115 (1.7%)	3	0/65 (0%)	0
Nervous system disorders
Headache	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Peripheral sensory neuropathy	6/115 (5.2%)	7	4/115 (3.5%)	4	1/65 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/115 (0.9%)	2	0/115 (0%)	0	0/65 (0%)	0
Rash desquamating	5/115 (4.3%)	7	2/115 (1.7%)	3	4/65 (6.2%)	4
Vascular disorders
Hypertension	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Hypotension	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Thrombosis	1/115 (0.9%)	2	0/115 (0%)	0	0/65 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I (THL)		Arm II (TH)		Arm III (TL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/115 (99.1%)		114/115 (99.1%)		64/65 (98.5%)
Blood and lymphatic system disorders
Blood disorder	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Febrile neutropenia	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Hemoglobin decreased	74/115 (64.3%)	232	72/115 (62.6%)	218	40/65 (61.5%)	114
Hemolysis	1/115 (0.9%)	4	0/115 (0%)	0	1/65 (1.5%)	1
Cardiac disorders
Cardiac disorder	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Left ventricular failure	4/115 (3.5%)	5	4/115 (3.5%)	5	0/65 (0%)	0
Myocardial ischemia	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Sinus bradycardia	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Sinus tachycardia	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Ear and labyrinth disorders
Tinnitus	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Eye disorders
Dry eye syndrome	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Eye disorder	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Vision blurred	2/115 (1.7%)	2	1/115 (0.9%)	1	1/65 (1.5%)	1
Watering eyes	0/115 (0%)	0	1/115 (0.9%)	3	0/65 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/115 (0%)	0	1/115 (0.9%)	2	0/65 (0%)	0
Abdominal pain	1/115 (0.9%)	3	2/115 (1.7%)	2	1/65 (1.5%)	2
Constipation	1/115 (0.9%)	1	6/115 (5.2%)	10	0/65 (0%)	0
Diarrhea	100/115 (87%)	307	55/115 (47.8%)	110	56/65 (86.2%)	148
Dyspepsia	3/115 (2.6%)	5	4/115 (3.5%)	9	2/65 (3.1%)	2
Ear, nose and throat examination abnormal	0/115 (0%)	0	1/115 (0.9%)	1	1/65 (1.5%)	1
Flatulence	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Hemorrhoids	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Mucositis oral	2/115 (1.7%)	2	3/115 (2.6%)	4	2/65 (3.1%)	2
Nausea	61/115 (53%)	136	45/115 (39.1%)	94	32/65 (49.2%)	66
Oral hemorrhage	2/115 (1.7%)	2	0/115 (0%)	0	0/65 (0%)	0
Toothache	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Vomiting	18/115 (15.7%)	28	13/115 (11.3%)	14	16/65 (24.6%)	23
General disorders
Chills	0/115 (0%)	0	0/115 (0%)	0	2/65 (3.1%)	3
Edema limbs	4/115 (3.5%)	5	6/115 (5.2%)	7	1/65 (1.5%)	2
Fatigue	101/115 (87.8%)	313	97/115 (84.3%)	319	47/65 (72.3%)	140
Fever	2/115 (1.7%)	2	1/115 (0.9%)	1	0/65 (0%)	0
General symptom	0/115 (0%)	0	1/115 (0.9%)	1	1/65 (1.5%)	1
Localized edema	1/115 (0.9%)	1	1/115 (0.9%)	1	0/65 (0%)	0
Pain	0/115 (0%)	0	2/115 (1.7%)	2	3/65 (4.6%)	6
Hepatobiliary disorders
Hepatobiliary disease	0/115 (0%)	0	1/115 (0.9%)	3	0/65 (0%)	0
Immune system disorders
Hypersensitivity	11/115 (9.6%)	16	14/115 (12.2%)	18	8/65 (12.3%)	9
Infections and infestations
Biliary tract infection	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Bladder infection	1/115 (0.9%)	1	0/115 (0%)	0	1/65 (1.5%)	1
Catheter related infection	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Colitis, infectious (e.g., Clostridium difficile)	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Device related infection	1/115 (0.9%)	1	2/115 (1.7%)	2	0/65 (0%)	0
Infection	1/115 (0.9%)	1	2/115 (1.7%)	3	1/65 (1.5%)	1
Mucosal infection	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Nail infection	0/115 (0%)	0	0/115 (0%)	0	2/65 (3.1%)	2
Pharyngitis	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Pneumonia	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Sinusitis	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Skin infection	0/115 (0%)	0	2/115 (1.7%)	2	0/65 (0%)	0
Upper respiratory infection	2/115 (1.7%)	2	1/115 (0.9%)	1	1/65 (1.5%)	1
Urinary tract infection	1/115 (0.9%)	1	0/115 (0%)	0	1/65 (1.5%)	1
Vaginal infection	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Wound infection	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Injury, poisoning and procedural complications
Fracture	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Intraoperative hepatobiliary injury	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Vascular access complication	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Wound dehiscence	1/115 (0.9%)	1	1/115 (0.9%)	2	0/65 (0%)	0
Investigations
Alanine aminotransferase increased	15/115 (13%)	26	9/115 (7.8%)	19	6/65 (9.2%)	6
Alkaline phosphatase increased	2/115 (1.7%)	4	0/115 (0%)	0	1/65 (1.5%)	1
Amylase increased	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Aspartate aminotransferase increased	12/115 (10.4%)	20	8/115 (7%)	14	4/65 (6.2%)	4
Blood bilirubin increased	2/115 (1.7%)	3	0/115 (0%)	0	0/65 (0%)	0
CD4 lymphocytes decreased	1/115 (0.9%)	1	1/115 (0.9%)	1	0/65 (0%)	0
Leukocyte count decreased	7/115 (6.1%)	11	6/115 (5.2%)	10	4/65 (6.2%)	7
Lymphocyte count decreased	1/115 (0.9%)	1	1/115 (0.9%)	2	0/65 (0%)	0
Neutrophil count decreased	41/115 (35.7%)	60	29/115 (25.2%)	51	19/65 (29.2%)	40
Platelet count decreased	2/115 (1.7%)	4	2/115 (1.7%)	4	3/65 (4.6%)	3
Weight gain	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Metabolism and nutrition disorders
Anorexia	2/115 (1.7%)	3	3/115 (2.6%)	6	1/65 (1.5%)	1
Blood glucose increased	2/115 (1.7%)	5	4/115 (3.5%)	11	2/65 (3.1%)	6
Dehydration	2/115 (1.7%)	3	0/115 (0%)	0	0/65 (0%)	0
Serum albumin decreased	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Serum calcium decreased	1/115 (0.9%)	3	0/115 (0%)	0	0/65 (0%)	0
Serum calcium increased	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Serum potassium decreased	8/115 (7%)	11	0/115 (0%)	0	4/65 (6.2%)	5
Serum potassium increased	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Serum sodium decreased	0/115 (0%)	0	1/115 (0.9%)	1	2/65 (3.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/115 (0.9%)	1	1/115 (0.9%)	1	1/65 (1.5%)	3
Arthritis	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Back pain	0/115 (0%)	0	1/115 (0.9%)	1	1/65 (1.5%)	1
Chest wall pain	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Myalgia	28/115 (24.3%)	49	34/115 (29.6%)	75	22/65 (33.8%)	38
Neck pain	1/115 (0.9%)	2	0/115 (0%)	0	0/65 (0%)	0
Nervous system disorders
Dizziness	0/115 (0%)	0	3/115 (2.6%)	3	1/65 (1.5%)	1
Dysgeusia	2/115 (1.7%)	2	1/115 (0.9%)	1	0/65 (0%)	0
Headache	4/115 (3.5%)	5	4/115 (3.5%)	8	1/65 (1.5%)	1
Peripheral motor neuropathy	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Peripheral sensory neuropathy	92/115 (80%)	229	84/115 (73%)	198	44/65 (67.7%)	125
Seizure	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Sinus pain	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Syncope	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Tremor	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Psychiatric disorders
Anxiety	1/115 (0.9%)	1	2/115 (1.7%)	4	1/65 (1.5%)	3
Depression	1/115 (0.9%)	2	1/115 (0.9%)	2	1/65 (1.5%)	1
Insomnia	6/115 (5.2%)	8	4/115 (3.5%)	7	3/65 (4.6%)	3
Libido decreased	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Renal and urinary disorders
Hemorrhage urinary tract	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Urinary frequency	2/115 (1.7%)	2	1/115 (0.9%)	1	1/65 (1.5%)	1
Urinary incontinence	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Urine discoloration	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	1
Reproductive system and breast disorders
Breast pain	1/115 (0.9%)	1	0/115 (0%)	0	2/65 (3.1%)	6
Irregular menstruation	2/115 (1.7%)	4	0/115 (0%)	0	0/65 (0%)	0
Vaginal discharge	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Vaginal dryness	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Vaginal pain	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/115 (0.9%)	1	1/115 (0.9%)	1	1/65 (1.5%)	3
Cough	2/115 (1.7%)	2	2/115 (1.7%)	2	2/65 (3.1%)	3
Dyspnea	2/115 (1.7%)	2	3/115 (2.6%)	4	2/65 (3.1%)	3
Epistaxis	3/115 (2.6%)	3	6/115 (5.2%)	8	4/65 (6.2%)	7
Laryngeal mucositis	1/115 (0.9%)	2	0/115 (0%)	0	0/65 (0%)	0
Nasal congestion	1/115 (0.9%)	1	1/115 (0.9%)	1	1/65 (1.5%)	1
Pharyngolaryngeal pain	2/115 (1.7%)	2	1/115 (0.9%)	1	0/65 (0%)	0
Respiratory tract hemorrhage	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Voice alteration	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	3
Skin and subcutaneous tissue disorders
Alopecia	6/115 (5.2%)	9	10/115 (8.7%)	23	1/65 (1.5%)	3
Dry skin	3/115 (2.6%)	3	2/115 (1.7%)	2	1/65 (1.5%)	1
Erythema multiforme	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	2
Hand-and-foot syndrome	1/115 (0.9%)	2	1/115 (0.9%)	1	0/65 (0%)	0
Nail disorder	5/115 (4.3%)	5	10/115 (8.7%)	10	4/65 (6.2%)	7
Pain of skin	1/115 (0.9%)	3	0/115 (0%)	0	0/65 (0%)	0
Photosensitivity	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	2
Pruritus	4/115 (3.5%)	5	1/115 (0.9%)	2	3/65 (4.6%)	3
Rash acneiform	5/115 (4.3%)	5	3/115 (2.6%)	3	1/65 (1.5%)	3
Rash desquamating	83/115 (72.2%)	243	49/115 (42.6%)	92	48/65 (73.8%)	137
Skin disorder	2/115 (1.7%)	3	3/115 (2.6%)	5	1/65 (1.5%)	1
Skin hyperpigmentation	0/115 (0%)	0	1/115 (0.9%)	1	0/65 (0%)	0
Skin induration	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Skin ulceration	1/115 (0.9%)	1	0/115 (0%)	0	0/65 (0%)	0
Vascular disorders
Flushing	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	2
Hemorrhage	0/115 (0%)	0	0/115 (0%)	0	1/65 (1.5%)	2
Hot flashes	1/115 (0.9%)	1	8/115 (7%)	12	1/65 (1.5%)	1
Hypertension	1/115 (0.9%)	1	4/115 (3.5%)	5	1/65 (1.5%)	1

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.