- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00667251
Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Santa Fe, Argentina, 3000
- Novartis Investigative Site
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Tucuman, Argentina, 4000
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Buenos Aires
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Capital Federal, Buenos Aires, Argentina, C1426ANZ
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Capital Federal, Buenos Aires, Argentina, C1405CUB
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
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La Plata, Buenos Aires, Argentina, B1920CMK
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Río Negro
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Cipolletti, Río Negro, Argentina, R8324EMB
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Viedma, Río Negro, Argentina, R8500ACE
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Santa Fe
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Rosario, Santa Fe, Argentina, S2000KZE
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Australian Capital Territory
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Garran, Australian Capital Territory, Australia, 2606
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New South Wales
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Liverpool, New South Wales, Australia, 2170
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North Sydney, New South Wales, Australia, 2060
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Tweed Heads, New South Wales, Australia, 2485
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Queensland
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Woolloongabba, Queensland, Australia, 4102
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South Australia
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Adelaide, South Australia, Australia, 5000
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Bedford Park, South Australia, Australia, 5042
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Kurralta Park, South Australia, Australia, 5037
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Tasmania
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Hobart, Tasmania, Australia, 7000
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Victoria
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Box Hill, Victoria, Australia, 3128
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Fitzroy, Victoria, Australia, 3065
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Wodonga, Victoria, Australia, 3690
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Western Australia
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Subiaco, Western Australia, Australia, 6008
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Gent, Belgium, 9000
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Jette, Belgium, 1090
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Liege, Belgium, 4000
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Namur, Belgium, 5000
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Quebec, Canada, G1S 4L8
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
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British Columbia
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Kelowna, British Columbia, Canada, V1Y 5L3
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Surrey, British Columbia, Canada, V3V 1Z2
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Vancouver, British Columbia, Canada, V5Z 4E6
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Victoria, British Columbia, Canada, V8R 6V5
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
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New Brunswick
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Moncton, New Brunswick, Canada, E1C 6Z8
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Saint John, New Brunswick, Canada, E2L 4L2
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Ontario
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Barrie, Ontario, Canada, L4M 6M2
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Hamilton, Ontario, Canada, L8V 5C2
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Kingston, Ontario, Canada, K7L 5P9
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London, Ontario, Canada, N6A 4L6
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Newmarket, Ontario, Canada, L3Y 2P9
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Ottawa, Ontario, Canada, K1H 8L6
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Sault Ste. Marie, Ontario, Canada, P6B 0A8
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St Catharines, Ontario, Canada, L2R 7C6
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Sudbury, Ontario, Canada, P3E 5J1
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Thunder Bay, Ontario, Canada, P7B 6V4
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Prince Edward Island
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Charlottetown, Prince Edward Island, Canada, C1A 8T5
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Quebec
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Montreal, Quebec, Canada, H2W 1S6
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Montreal, Quebec, Canada, H1T 2M4
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Montreal, Quebec, Canada, H2L 4M1
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Saskatchewan
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Regina, Saskatchewan, Canada, S4T 7T1
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Saskatoon, Saskatchewan, Canada, S7N 4H4
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Angers, France, 49033
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Bordeaux, France, 33075
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Bordeaux, France, 33077
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Caen Cedex 05, France, 14076
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Marseille cedex 9, France, 13273
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Metz-Tessy, France, 74370
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Nantes cedex, France, 44202
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Paris, France, 75014
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Strasbourg, France, 67085
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Berlin, Germany, 10117
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Berlin, Germany, 10367
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Brandenburg, Germany, 14770
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Hamburg, Germany, 22081
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Hamburg, Germany, 20095
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Hamburg, Germany, 22767
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Baden-Wuerttemberg
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Heidelberg, Baden-Wuerttemberg, Germany, 69115
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Stuttgart, Baden-Wuerttemberg, Germany, 70190
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Bayern
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Coburg, Bayern, Germany, 96450
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Eggenfelden, Bayern, Germany, 84307
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Fuerth, Bayern, Germany, 90766
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Regensburg, Bayern, Germany, 93049
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Rosenheim, Bayern, Germany, 83022
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Weiden, Bayern, Germany, 92637
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Brandenburg
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Fuerstenwalde, Brandenburg, Germany, 15517
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Hessen
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Frankfurt, Hessen, Germany, 60596
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Fulda, Hessen, Germany, 36043
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Lich, Hessen, Germany, 35423
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Niedersachsen
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Goslar, Niedersachsen, Germany, 38642
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Hannover, Niedersachsen, Germany, 30559
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Leer, Niedersachsen, Germany, 26789
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Nordrhein-Westfalen
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Bielefeld, Nordrhein-Westfalen, Germany, 33611
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Bonn, Nordrhein-Westfalen, Germany, 53113
- Novartis Investigative Site
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Coesfeld, Nordrhein-Westfalen, Germany, 48653
- Novartis Investigative Site
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Essen, Nordrhein-Westfalen, Germany, 45122
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Koeln, Nordrhein-Westfalen, Germany, 51067
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Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
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Troisdorf, Nordrhein-Westfalen, Germany, 53840
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Velbert, Nordrhein-Westfalen, Germany, 42551
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Witten, Nordrhein-Westfalen, Germany, 58452
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Rheinland-Pfalz
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Koblenz, Rheinland-Pfalz, Germany, 56068
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Saarland
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Saarbruecken, Saarland, Germany, 66113
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Sachsen
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Dresden, Sachsen, Germany, 01127
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Sachsen-Anhalt
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Halle, Sachsen-Anhalt, Germany, 06120
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Schleswig-Holstein
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Luebeck, Schleswig-Holstein, Germany, 23538
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Bangalore, India, 560038
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Nagpur, India, 440010
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Pune, India, 411001
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Beer-Sheva, Israel, 84101
- Novartis Investigative Site
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Holon, Israel, 58100
- Novartis Investigative Site
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Petah-Tikva, Israel, 49100
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Poriya, Israel, 15208
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Ramat Gan, Israel, 52621
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Chieti, Italy, 66100
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Friuli-Venezia-Giulia
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Aviano (pn), Friuli-Venezia-Giulia, Italy, 33081
- Novartis Investigative Site
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Lazio
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Roma, Lazio, Italy, 00189
- Novartis Investigative Site
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Sora (FR), Lazio, Italy, 03039
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Liguria
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Genova, Liguria, Italy, 16132
- Novartis Investigative Site
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Puglia
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Lecce, Puglia, Italy, 73100
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Sardegna
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Sassari, Sardegna, Italy, 07100
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Toscana
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Prato (PO), Toscana, Italy, 59100
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Aichi, Japan, 464-8681
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Chiba, Japan, 277-8577
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Ehime, Japan, 791-0280
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Kagoshima, Japan, 892-0833
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Kanagawa, Japan, 241-8515
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Osaka, Japan, 540-0006
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Osaka, Japan, 565-0871
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Saitama, Japan, 350-1298
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Saitama, Japan, 362-0806
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Shizuoka, Japan, 411-8777
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Tokyo, Japan, 104-8560
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Tokyo, Japan, 113-8677
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Gyeonggi-do, Korea, Republic of, 10408
- Novartis Investigative Site
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Gyeonggi-do, Korea, Republic of, 410-769
- Novartis Investigative Site
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Seoul, Korea, Republic of, 03722
- Novartis Investigative Site
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Seoul, Korea, Republic of, 120-752
- Novartis Investigative Site
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Seoul, Korea, Republic of, 110-744
- Novartis Investigative Site
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Songpa-gu, Seoul, Korea, Republic of, 138-736
- Novartis Investigative Site
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Mexico City, Mexico, CP 14080
- Novartis Investigative Site
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Morelos
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Cuernavaca, Morelos, Mexico, 62450
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Sonora
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Ciudad Obregon, Sonora, Mexico, 85000
- Novartis Investigative Site
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Amsterdam, Netherlands, 1091 AC
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Delft, Netherlands, 2625 AD
- Novartis Investigative Site
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Dordrecht, Netherlands, 3318 AT
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Maastricht, Netherlands, 6229 HX
- Novartis Investigative Site
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Gdansk, Poland, 80-219
- Novartis Investigative Site
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Lodz, Poland, 93-509
- Novartis Investigative Site
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Olsztyn, Poland, 10-226
- Novartis Investigative Site
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Olsztyn, Poland, 10-513
- Novartis Investigative Site
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Plock, Poland, 09-400
- Novartis Investigative Site
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Rzeszow, Poland, 35-021
- Novartis Investigative Site
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Warszawa, Poland, 02-781
- Novartis Investigative Site
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Warszawa, Poland, 04-125
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Arkhangelsk, Russian Federation, 163045
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Ivanovo, Russian Federation, 153013
- Novartis Investigative Site
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Kazan, Russian Federation, 420029
- Novartis Investigative Site
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Kirov, Russian Federation, 610021
- Novartis Investigative Site
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Lipetsk, Russian Federation, 398005
- Novartis Investigative Site
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Moscow, Russian Federation, 115 478
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Ryazan, Russian Federation, 390011
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St. Petersburg, Russian Federation, 197758
- Novartis Investigative Site
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St. Petersburg, Russian Federation, 197022
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Stavropol, Russian Federation, 355047
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Ufa, Russian Federation, 450054
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Ufa,, Russian Federation, 450054
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Alcorcon, Spain, 28922
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Alicante, Spain, 03010
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Badalona, Spain, 08916
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Barcelona, Spain, 08036
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Elche, Spain, 03202
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Girona, Spain, 17007
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Jaen, Spain, 23007
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La Coruna, Spain, 15009
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Lugo, Spain, 27003
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Madrid, Spain, 28034
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Madrid, Spain, 28007
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Madrid, Spain, 28040
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Majadahonda (Madrid), Spain, 28222
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Pozuelo De Alarcon (Madrid), Spain, 28223
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Sevilla, Spain, 41013
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Valencia, Spain, 46009
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Changhua, Taiwan, 500
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Taichung, Taiwan, 404
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Tainan County, Taiwan, 736
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Taipei, Taiwan, 100
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Taipei, Taiwan, 112
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Bangkok, Thailand, 10700
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Chiangmai, Thailand, 50200
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Dnepropetrovsk, Ukraine, 49102
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Dnipropetrovsk, Ukraine, 49100
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Lviv, Ukraine, 79031
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Sumy, Ukraine, 40005
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Bournemouth, United Kingdom, BH7 7DW
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Brighton, United Kingdom, BN2 5BE
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Chelmsford, United Kingdom, CM1 7ET
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Cheltenham, United Kingdom, GL53 7AN
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Colchester, United Kingdom, CO3 3NB
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Cottingham, Hull, United Kingdom, HU16 5JQ
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Derby, United Kingdom, DE22 3NE
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Edmonton, United Kingdom, N18 1QX
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Guildford, United Kingdom, GU2 7XX
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Harrogate, United Kingdom, HG2 7SX
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Huddersfield, United Kingdom, HD3 3EA
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London, United Kingdom, SW3 6JJ
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Newcastle upon Tyne, United Kingdom, NE7 7DN
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Norwich, United Kingdom, NR4 7UY
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Nottingham, United Kingdom, NG5 1PB
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Oxford, United Kingdom, OX3 7LJ
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Poole, Dorset, United Kingdom, BH15 2JB
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Sheffield, United Kingdom, S10 2SJ
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Shrewsbury, United Kingdom, SY3 8XQ
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Sutton, United Kingdom, SM2 5PT
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Whitchurch, Cardiff, United Kingdom, CF14 2TL
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York, United Kingdom, YO31 8HE
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Alaska
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Anchorage, Alaska, United States, 99508
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Arizona
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Tucson, Arizona, United States, 85715
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Arkansas
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Hot Springs, Arkansas, United States, 71913
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California
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Berkeley, California, United States, 94704
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Highland, California, United States, 92346
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Montebello, California, United States, 90640
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Colorado
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Colorado Springs, Colorado, United States, 80907
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Denver, Colorado, United States, 80204
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Connecticut
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Greenwich, Connecticut, United States, 06830
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Southington, Connecticut, United States, 06489
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Stamford, Connecticut, United States, 06902-3628
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Trumbull, Connecticut, United States, 06611
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Waterbury, Connecticut, United States, 06708
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Florida
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Kissimmee, Florida, United States, 34741
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Loxahatchee Groves, Florida, United States, 33470
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New Port Richey, Florida, United States, 34655
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Georgia
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Augusta, Georgia, United States, 30901
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Lawrenceville, Georgia, United States, 30046
- Novartis Investigative Site
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Savannah, Georgia, United States, 31405
- Novartis Investigative Site
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Idaho
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Post Falls, Idaho, United States, 83854
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Illinois
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Chicago, Illinois, United States, 60657
- Novartis Investigative Site
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Oak Lawn, Illinois, United States, 60453
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Indiana
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Evansville, Indiana, United States, 47713
- Novartis Investigative Site
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Goshen, Indiana, United States, 46526
- Novartis Investigative Site
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Indianapolis, Indiana, United States, 46237
- Novartis Investigative Site
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Munster, Indiana, United States, 46321
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New Albany, Indiana, United States, 47150
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Maryland
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Towson, Maryland, United States, 21204
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Wheaton, Maryland, United States, 20902
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Montana
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Bozeman, Montana, United States, 59715
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Nebraska
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Grand Island, Nebraska, United States, 68803
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Kearney, Nebraska, United States, 68845
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Kearney, Nebraska, United States, 68847
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New Jersey
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Denville, New Jersey, United States, 07834
- Novartis Investigative Site
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Parsippany, New Jersey, United States, 07054
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New York
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Cooperstown, New York, United States, 13326
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North Carolina
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Greensboro, North Carolina, United States, 27403
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Ohio
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Canton, Ohio, United States, 44718
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Wooster, Ohio, United States, 44691
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Oregon
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Portland, Oregon, United States, 97227
- Novartis Investigative Site
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15212-4772
- Novartis Investigative Site
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South Carolina
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Columbia, South Carolina, United States, 29210
- Novartis Investigative Site
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Tennessee
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Memphis, Tennessee, United States, 38120
- Novartis Investigative Site
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Virginia
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Chesapeake, Virginia, United States, 23320
- Novartis Investigative Site
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Salem, Virginia, United States, 24153
- Novartis Investigative Site
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Washington
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Bellevue, Washington, United States, 98004
- Novartis Investigative Site
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Kirkland, Washington, United States, 98034
- Novartis Investigative Site
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Mount Vernon, Washington, United States, 98273
- Novartis Investigative Site
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Seattle, Washington, United States, 98109
- Novartis Investigative Site
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Sequim, Washington, United States, 98382
- Novartis Investigative Site
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Tacoma, Washington, United States, 98405
- Novartis Investigative Site
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Wenatchee, Washington, United States, 98801
- Novartis Investigative Site
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Lapatinib
Plus taxane based chemotherapy
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75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).
1250 mg po daily (while given with taxane).
1500mg PO daily (when given alone after taxane completion).
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
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Active Comparator: Trastuzumab
Plus taxane based chemotherapy.
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75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: From randomization to RECIST V 1.0 progression or death assessed up to 39 months.
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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
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From randomization to RECIST V 1.0 progression or death assessed up to 39 months.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: From randomization to death from any cause, assessed up to 44 months.
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OS median follow-up not achieved; estimated with quartile estimates
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From randomization to death from any cause, assessed up to 44 months.
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Time to CNS Metastases at the Time of First Progression
Time Frame: From randomization to CNS metastases at time of first progression, assessed up to 39 months.
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From randomization to CNS metastases at time of first progression, assessed up to 39 months.
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CNS Metastases at the Time of Progression (ITT)
Time Frame: Incidence rate of CNS metastases at first progression assessed up to 39 months
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Incidence rate of CNS metastases at first progression assessed up to 39 months
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CNS Metastases at the Time of Progression (HER2+)
Time Frame: Incidence rate of CNS mestastes at first progression, assessed up to 39 months
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Incidence rate of CNS mestastes at first progression, assessed up to 39 months
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Overall Objective Response Rate (Complete or Partial) ITT
Time Frame: 4 years
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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).
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4 years
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Overall Objective Response Rate (Complete or Partial) HER2/Neu+
Time Frame: Median follow-up of 21.5 months.
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Response determined by RECIST V 1.0
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Median follow-up of 21.5 months.
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Clinical Benefit Response Rate (ITT)
Time Frame: 24 weeks
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Best overall response of CR, PR or stable disease at end of week 24.
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24 weeks
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Clinical Benefit Response Rate (HER2/Neu+))
Time Frame: 24 weeks
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Best overall response of CR, PR, or stable disease at end of week 24.
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24 weeks
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Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks
Time Frame: 12 weeks
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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
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12 weeks
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Effects of Changes in Biomarkers on Clinical Outcomes
Time Frame: Not available at this time
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Not available at this time
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Economic Evaluation, Including Health Utilities, as Measured by the EQ-5D Questionnaire, and Healthcare Utilization
Time Frame: Not available at this time
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Not available at this time
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Liu S, Chen B, Burugu S, Leung S, Gao D, Virk S, Kos Z, Parulekar WR, Shepherd L, Gelmon KA, Nielsen TO. Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2017 Nov 9;3(11):e172085. doi: 10.1001/jamaoncol.2017.2085. Epub 2017 Nov 9.
- Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. doi: 10.1200/JCO.2014.56.9590. Epub 2015 Mar 16.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Docetaxel
- Paclitaxel
- Trastuzumab
- Lapatinib
Other Study ID Numbers
- 108919
- CLAP016A2303 (Other Identifier: Novartis)
- CAN-NCIC-MA31 (Other Grant/Funding Number: NCI US - Physician Data Query)
- 2007-004568-27 (EudraCT Number)
- CDR0000594764 (Other Identifier: PDQ)
- EGF108919 (Other Identifier: GSK)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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