Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00667251
• Other study ID #: 108919
• Secondary ID: CLAP016A2303CAN-
• Status: Completed
• Phase: Phase 3
• Start date: October 7, 2008
• Est. completion date: July 27, 2022

Study information

• Verified date: July 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: HER2/neu is a receptor (protein) which is found in unusually high amounts in approximately 1 in 5 cancer patients. Scientific evidence suggests that having high amounts of the HER2/neu receptor is important for breast cancer to grow and spread. Women with previously untreated metastatic breast cancer (breast cancer that has spread to other organs) and with high levels of the HER2/neu receptor receive as their usual treatment chemotherapy with one of the approved chemotherapy drugs paclitaxel or docetaxel (called "taxanes") together with another approved drug called "trastuzumab". Chemotherapy drugs, such as paclitaxel and docetaxel, work either by killing tumour cells or by stopping them from dividing. Trastuzumab is an antibody that is given through a vein in the arm and it works by specifically "targeting" the HER2/neu i.e. it attaches to it and "turns it off". Although some of the patients who receive this taxane plus trastuzumab treatment feel better for some months, the cancer usually starts to grow again. Lapatinib is a new drug. Like trastuzumab, it also works by specifically "targeting" the HER2/neu receptor, but it does so in a different way. Lapatinib is not an antibody. It is a pill that is taken daily by mouth. Because lapatinib works in a different way than trastuzumab, it may be worse, as good as or better than trastuzumab in keeping metastatic HER/neu positive cancer from growing. However, this is not known.

Purpose: This randomized Phase III trial is comparing chemotherapy (a taxane) given together with lapatinib with chemotherapy (a taxane) given together with trastuzumab in women with HER2/neu positive breast cancer.

Description:

OBJECTIVES:

Primary

• To compare the progression-free survival of women with HER2/neu-positive metastatic breast cancer treated with taxane-based chemotherapy in combination with lapatinib ditosylate or trastuzumab (Herceptin®).

Secondary

• To compare the overall survival.

• To compare the time to CNS metastases at the time of first progression.

• To compare the incidence rates of CNS metastases at the time of progression.

• To compare the overall objective response rate (complete or partial response), time to response, and duration of response in patients with measurable disease at baseline.

• To compare the clinical benefit response rate.

• To compare the adverse event profile.

• To compare the quality of life.

• To compare clinical outcomes using biomarker changes in biological samples.

• To compare health economics, including healthcare utilization and health utilities.

OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant/adjuvant anti-HER2/neu-targeted therapy (yes vs no), prior neoadjuvant/adjuvant taxane chemotherapy (yes vs no), planned taxane therapy (paclitaxel vs docetaxel), and liver metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive either paclitaxel IV on days 1, 8, and 15; treatment with paclitaxel repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV on day 1; treatment with docetaxel repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients on docetaxel also receive filgrastim (G-CSF) according to institutional standard. All patients receive oral lapatinib ditosylate once daily during taxane treatment and continue after completion of taxane treatment, in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive paclitaxel IV on days 1, 8, and 15 and trastuzumab (Herceptin®) IV on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV and trastuzumab IV on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of taxane chemotherapy and trastuzumab, all patients receive trastuzumab alone IV once every 3 weeks in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue samples are analyzed for ER, PgR, EGFR, CK5/6, Ki67, and other molecular biomarkers by tissue microarray and immunohistochemistry.

Patients complete quality of life questionnaires (EORTC QLQ-C30 and a Trial Specific Checklist) at baseline, every 12 weeks for 96 weeks, and then every 24 weeks until disease progression.

After completion of study treatment, patients are followed at 4 weeks post treatment, and then every 12 weeks thereafter (counting from the beginning of study therapy).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 652
• Est. completion date: July 27, 2022
• Est. primary completion date: August 1, 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Metastatic (stage IV) disease at primary diagnosis or at relapse after curative intent therapy

• Local or central laboratory confirmedHER2/neu* overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by the following:

• 3+ overexpression (in > 30% of invasive tumor cells) by immunohistochemistry (IHC)

• 2+ or 3+ overexpression (in = 30% of invasive tumor cells) by IHC AND demonstrates HER2/neu gene amplification by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)

• HER2/neu gene amplification by FISH/CISH (> 6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio [HER2 gene copies to chromosome 17 signals] of = 2.2) NOTE: *Patients with a negative or equivocal overall result (FISH/CISH ratio of < 2.2, = 6.0 HER2/neu gene copies per nucleus, or staining scores of 0, 1+, 2+, or 3+ [in = 30% of neoplastic cells] by IHC) are not eligible

• Formalin-fixed paraffin-embedded tumor specimen available

• No CNS metastases (including leptomeningeal involvement)

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy > 6 months

• Absolute granulocyte count > 1,500/mm³

• Platelet count > 75,000/mm³

• Hemoglobin > 10 g/dL

• Serum creatinine = 2.0 times upper limit of normal (ULN)

• Total bilirubin = 1.5 times ULN (< 3 times ULN for patients with Gilbert's disease)

• AST and/or ALT = 2.5 times ULN (< 5 times ULN for patients planning to receive paclitaxel-based therapy)

• LVEF = 50% by MUGA or ECHO

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Must be accessible for study treatment and follow-up

• No history of other malignancies, except adequately treated ductal carcinoma in situ or lobular carcinoma in situ, adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor (non-breast) with no evidence of disease for = 5 years

• No serious cardiac illness or condition including, but not limited to, any of the following:

• History of documented congestive heart failure

• Systolic dysfunction (LVEF < 50%)

• High-risk uncontrolled arrhythmias (i.e., ventricular tachycardia, high-grade atrioventricular block, or supraventricular arrhythmias that are not adequately rate-controlled)

• Unstable angina pectoris requiring anti-anginal medication

• Clinically significant valvular heart disease

• Evidence of transmural infarction on ECG

• Inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)

• New York Heart Association class III-IV functional status

• No serious illness or medical condition that would not allow the patient to be managed according to the protocol including, but not limited to, any of the following:

• History of significant neurologic or psychiatric disorder that would impair the ability to obtain informed consent or limit compliance with study requirements

• Active uncontrolled infection

• Serious or nonhealing wound, ulcer, or bone fracture

• No peripheral neuropathy = grade 2

• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication including, but not limited to, any of the following:

• Malabsorption syndrome

• Requirement for IV alimentation

• Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

• No history of allergic or hypersensitivity reactions to any study drug or their excipients or to compounds with similar chemical composition to any of the study drugs

• Prior allergic reactions to taxanes are allowed provided they were adequately treated and, according to the treating physician, would not prohibit further treatment with taxanes

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy

• No prior chemotherapy, immunotherapy, biological therapy, or anti-HER2/neu-targeted therapy for recurrent or metastatic breast cancer

• At least 12 months since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting

• At least 12 months since prior anti-HER2/neu-targeted therapy in the neoadjuvant or adjuvant setting

• Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, or metastatic setting allowed

• At least 2 weeks since prior radiotherapy in the adjuvant or metastatic setting

• Prior radiotherapy to a solitary metastatic lesion allowed provided there is documented disease progression after completion of radiotherapy

• More than 30 days (or 5 half-lives) since prior investigational drugs

• At least 7 days since prior and no concurrent CYP3A4 inhibitors (6 months for amiodarone)

• At least 14 days since prior and no concurrent CYP3A4 inducers

• No prior surgical procedures affecting absorption (e.g., resection of stomach or small bowel)

• No concurrent palliative radiotherapy

• No other concurrent anticancer treatment

• No other concurrent investigational drugs for breast cancer

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab
IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).

Drug:
• docetaxel
75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).
• lapatinib ditosylate
1250 mg po daily (while given with taxane). 1500mg PO daily (when given alone after taxane completion).
• paclitaxel
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Argentina	Novartis Investigative Site	Cipolletti	Río Negro
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Argentina	Novartis Investigative Site	Viedma	Río Negro
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Fitzroy	Victoria
Australia	Novartis Investigative Site	Garran	Australian Capital Territory
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Kurralta Park	South Australia
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	North Sydney	New South Wales
Australia	Novartis Investigative Site	Subiaco	Western Australia
Australia	Novartis Investigative Site	Tweed Heads	New South Wales
Australia	Novartis Investigative Site	Wodonga	Victoria
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Jette
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Namur
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Charlottetown	Prince Edward Island
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Kelowna	British Columbia
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Newmarket	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Regina	Saskatchewan
Canada	Novartis Investigative Site	Saint John	New Brunswick
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Sault Ste. Marie	Ontario
Canada	Novartis Investigative Site	St Catharines	Ontario
Canada	Novartis Investigative Site	Sudbury	Ontario
Canada	Novartis Investigative Site	Surrey	British Columbia
Canada	Novartis Investigative Site	Thunder Bay	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoria	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Caen Cedex 05
France	Novartis Investigative Site	Marseille cedex 9
France	Novartis Investigative Site	Metz-Tessy
France	Novartis Investigative Site	Nantes cedex
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bonn	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Brandenburg
Germany	Novartis Investigative Site	Coburg	Bayern
Germany	Novartis Investigative Site	Coesfeld	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Dresden	Sachsen
Germany	Novartis Investigative Site	Eggenfelden	Bayern
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Frankfurt	Hessen
Germany	Novartis Investigative Site	Fuerstenwalde	Brandenburg
Germany	Novartis Investigative Site	Fuerth	Bayern
Germany	Novartis Investigative Site	Fulda	Hessen
Germany	Novartis Investigative Site	Goslar	Niedersachsen
Germany	Novartis Investigative Site	Halle	Sachsen-Anhalt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Koblenz	Rheinland-Pfalz
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Leer	Niedersachsen
Germany	Novartis Investigative Site	Lich	Hessen
Germany	Novartis Investigative Site	Luebeck	Schleswig-Holstein
Germany	Novartis Investigative Site	Porta Westfalica	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Regensburg	Bayern
Germany	Novartis Investigative Site	Rosenheim	Bayern
Germany	Novartis Investigative Site	Saarbruecken	Saarland
Germany	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Troisdorf	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Velbert	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Weiden	Bayern
Germany	Novartis Investigative Site	Witten	Nordrhein-Westfalen
India	Novartis Investigative Site	Bangalore
India	Novartis Investigative Site	Nagpur
India	Novartis Investigative Site	Pune
Israel	Novartis Investigative Site	Beer-Sheva
Israel	Novartis Investigative Site	Holon
Israel	Novartis Investigative Site	Petah-Tikva
Israel	Novartis Investigative Site	Poriya
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Aviano (pn)	Friuli-Venezia-Giulia
Italy	Novartis Investigative Site	Chieti
Italy	Novartis Investigative Site	Genova	Liguria
Italy	Novartis Investigative Site	Lecce	Puglia
Italy	Novartis Investigative Site	Prato (PO)	Toscana
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Sassari	Sardegna
Italy	Novartis Investigative Site	Sora (FR)	Lazio
Japan	Novartis Investigative Site	Aichi
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Ehime
Japan	Novartis Investigative Site	Kagoshima
Japan	Novartis Investigative Site	Kanagawa
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Shizuoka
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Korea, Republic of	Novartis Investigative Site	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Songpa-gu, Seoul
Mexico	Novartis Investigative Site	Ciudad Obregon	Sonora
Mexico	Novartis Investigative Site	Cuernavaca	Morelos
Mexico	Novartis Investigative Site	Mexico City
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Delft
Netherlands	Novartis Investigative Site	Dordrecht
Netherlands	Novartis Investigative Site	Maastricht
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Plock
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Arkhangelsk
Russian Federation	Novartis Investigative Site	Ivanovo
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Kirov
Russian Federation	Novartis Investigative Site	Lipetsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Russian Federation	Novartis Investigative Site	Ufa
Russian Federation	Novartis Investigative Site	Ufa,
Spain	Novartis Investigative Site	Alcorcon
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigative Site	Badalona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Elche
Spain	Novartis Investigative Site	Girona
Spain	Novartis Investigative Site	Jaen
Spain	Novartis Investigative Site	La Coruna
Spain	Novartis Investigative Site	Lugo
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Majadahonda (Madrid)
Spain	Novartis Investigative Site	Pozuelo De Alarcon (Madrid)
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Valencia
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan County
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiangmai
Ukraine	Novartis Investigative Site	Dnepropetrovsk
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Sumy
United Kingdom	Novartis Investigative Site	Bournemouth
United Kingdom	Novartis Investigative Site	Brighton
United Kingdom	Novartis Investigative Site	Chelmsford
United Kingdom	Novartis Investigative Site	Cheltenham
United Kingdom	Novartis Investigative Site	Colchester
United Kingdom	Novartis Investigative Site	Cottingham, Hull
United Kingdom	Novartis Investigative Site	Derby
United Kingdom	Novartis Investigative Site	Edmonton
United Kingdom	Novartis Investigative Site	Guildford
United Kingdom	Novartis Investigative Site	Harrogate
United Kingdom	Novartis Investigative Site	Huddersfield
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Poole, Dorset
United Kingdom	Novartis Investigative Site	Sheffield
United Kingdom	Novartis Investigative Site	Shrewsbury
United Kingdom	Novartis Investigative Site	Sutton
United Kingdom	Novartis Investigative Site	Whitchurch, Cardiff
United Kingdom	Novartis Investigative Site	York
United States	Novartis Investigative Site	Anchorage	Alaska
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Bellevue	Washington
United States	Novartis Investigative Site	Berkeley	California
United States	Novartis Investigative Site	Bozeman	Montana
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Chesapeake	Virginia
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Cooperstown	New York
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denville	New Jersey
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigative Site	Goshen	Indiana
United States	Novartis Investigative Site	Grand Island	Nebraska
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greenwich	Connecticut
United States	Novartis Investigative Site	Highland	California
United States	Novartis Investigative Site	Hot Springs	Arkansas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Kearney	Nebraska
United States	Novartis Investigative Site	Kearney	Nebraska
United States	Novartis Investigative Site	Kirkland	Washington
United States	Novartis Investigative Site	Kissimmee	Florida
United States	Novartis Investigative Site	Lawrenceville	Georgia
United States	Novartis Investigative Site	Loxahatchee Groves	Florida
United States	Novartis Investigative Site	Memphis	Tennessee
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Montebello	California
United States	Novartis Investigative Site	Mount Vernon	Washington
United States	Novartis Investigative Site	Munster	Indiana
United States	Novartis Investigative Site	New Albany	Indiana
United States	Novartis Investigative Site	New Port Richey	Florida
United States	Novartis Investigative Site	Oak Lawn	Illinois
United States	Novartis Investigative Site	Parsippany	New Jersey
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Post Falls	Idaho
United States	Novartis Investigative Site	Salem	Virginia
United States	Novartis Investigative Site	Savannah	Georgia
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sequim	Washington
United States	Novartis Investigative Site	Southington	Connecticut
United States	Novartis Investigative Site	Stamford	Connecticut
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Towson	Maryland
United States	Novartis Investigative Site	Trumbull	Connecticut
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Waterbury	Connecticut
United States	Novartis Investigative Site	Wenatchee	Washington
United States	Novartis Investigative Site	Wheaton	Maryland
United States	Novartis Investigative Site	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From randomization to RECIST V 1.0 progression or death assessed up to 39 months.
Secondary	Overall Survival	OS median follow-up not achieved; estimated with quartile estimates	From randomization to death from any cause, assessed up to 44 months.
Secondary	Time to CNS Metastases at the Time of First Progression		From randomization to CNS metastases at time of first progression, assessed up to 39 months.
Secondary	CNS Metastases at the Time of Progression (ITT)		Incidence rate of CNS metastases at first progression assessed up to 39 months
Secondary	CNS Metastases at the Time of Progression (HER2+)		Incidence rate of CNS mestastes at first progression, assessed up to 39 months
Secondary	Overall Objective Response Rate (Complete or Partial) ITT	Patients included in this assessment must have had at least one measurable lesion at baseline, and had at least one RECIST re-evaluation after baseline while on protocol therapy, prior to, or on, date of progression. Best overall response was classified to be Complete Response (CR) or Partial Response (PR).	4 years
Secondary	Overall Objective Response Rate (Complete or Partial) HER2/Neu+	Response determined by RECIST V 1.0	Median follow-up of 21.5 months.
Secondary	Clinical Benefit Response Rate (ITT)	Best overall response of CR, PR or stable disease at end of week 24.	24 weeks
Secondary	Clinical Benefit Response Rate (HER2/Neu+))	Best overall response of CR, PR, or stable disease at end of week 24.	24 weeks
Secondary	Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks	The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. The global score ranges from 0-100, with higher values representing a better quality of life. At 12 weeks: Group mean difference between arms	12 weeks
Secondary	Effects of Changes in Biomarkers on Clinical Outcomes		Not available at this time
Secondary	Economic Evaluation, Including Health Utilities, as Measured by the EQ-5D Questionnaire, and Healthcare Utilization		Not available at this time