- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT00331630
Abraxane and Lapatinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
RATIONALE: Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving Abraxane together with lapatinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving Abraxane together with lapatinib works in treating patients with stage I, stage II, or stage III breast cancer.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
OBJECTIVES:
Primary
- Determine the clinical response rate, as measured by clinical exam and imaging studies, in patients with stage I-III breast cancer treated with neoadjuvant Abraxane in combination with lapatinib.
Secondary
- Determine the pathologic complete response rate in patients treated with this regimen.
- Correlate proliferation (Ki67), apoptosis (cleaved caspase-3), and angiogenesis (vW, CD34) markers, measured before and after treatment, with tumor response in these patients.
- Conduct other correlative studies, including epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β), before and after treatment with this regimen to assess tumor response in these patients.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a pilot study. Patients are assigned to 1 of 2 treatment groups.
- Group 1: The first 10 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Group 2: The next 20 patients receive Abraxane and lapatinib (at a higher dose) as in group 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection and tumor biopsies periodically for correlative biomarker studies.
PROJECTED ACCRUAL: A total of 30 patients will be accrued to this study.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 1. korai fázis
Kapcsolatok és helyek
Tanulmányi helyek
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Illinois
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Chicago, Illinois, Egyesült Államok, 60611-3013
- Northwestern University, Northwestern Medical Faculty Foundation
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Chicago, Illinois, Egyesült Államok, 60611
- Hematology-Oncology Associates of Illinois
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Joliet, Illinois, Egyesült Államok, 60432
- Midwest Center for Hematology/Oncology
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Olympia Fields, Illinois, Egyesült Államok, 60461
- Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
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Texas
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Lubbock, Texas, Egyesült Államok, 79410-1894
- Joe Arrington Cancer Research and Treatment Center
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
DISEASE CHARACTERISTICS:
Histologically confirmed breast cancer
- Clinical stage I-III disease
- Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm with spiral CT scan
- HER2/neu 3+ by immunohistochemistry or positive by fluorescent in situ hybridization
- No known brain metastases
- Hormone receptor status unspecified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Male or female
- Life expectancy > 12 weeks
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500 mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- LVEF ≥ 50% as measured by echocardiogram or MUGA scan
- No other malignancy within the past year
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow and retain oral medication
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
- No ongoing or active infection
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No gastrointestinal (GI) tract disease that would preclude ability to take oral medication
- No malabsorption syndrome
- No requirement for IV alimentation
- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, immunotherapy, radiotherapy, or hormonal therapy for breast cancer
- No prior treatment with epidermal growth factor receptor targeting therapies
- No prior surgical procedures affecting absorption
- No prior surgery for breast cancer
At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
Dexamethasone or dexamethasone equivalent dose ≥ 1.5 mg/day, including any of the following:
- Cortisone (≥ 50 mg/day)
- Hydrocortisone (≥ 40 mg/day)
- Prednisone (≥ 10 mg/day)
- Methylprednisolone (≥ 8 mg/day)
- Phenytoin
- Carbamazepine
- Phenobarbital
- Efavirenz
- Nevirapine
- Rifampin
- Rifabutin
- Rifapentine
- Hypericum perforatum (St. John's wort)
- Modafinil
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
- Clarithromycin
- Erythromycin
- Troleandomycin
- Delavirdine
- Ritonavir
- Indinavir
- Saquinavir
- Nelfinavir
- Amprenavir
- Lopinavir
- Itraconazole
- Ketoconazole
- Voriconazole
- Fluconazole (doses up to 150 mg/day are permitted)
- Nefazodone
- Fluvoxamine
- Verapamil
- Diltiazem
- Cimetidine
- Aprepitant
- Grapefruit or its juice
- At least 6 months since prior and no concurrent amiodarone
At least 2 days since prior and no concurrent gastric pH modifiers*, including any of the following:
- Cimetidine
- Ranitidine
- Nizatidine
- Famotidine
- Omeprazole
- Esomeprazole
- Rabeprazole
- Pantoprazole
- Lansoprazole
- NOTE: *Antacids are allowed within 1 hour before and after administration of study drug
- No other concurrent investigational agents
- No other concurrent anticancer therapy, including chemotherapy, radiotherapy, immunotherapy, or antitumor hormonal therapy
- No concurrent herbal (alternative) medicines
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent bisphosphonates allowed
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
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Kísérleti: Treatment arm
30 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
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Oral lapatinib is taken once daily on days 1-21 of each treatment cycle.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Más nevek:
30 patients receive Abraxane IV over 30 minutes on day 1 each of each treatment cycle.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Más nevek:
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Clinical Response Rate (cRR)
Időkeret: At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)
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cRR measured by RECIST for target lesions assessed by clinical exam+ mammogram+ ultrasound (US). cRR is defined as number of patients who's best response in any of the assessments (clinical exam/mammogram/US) is CR+PR. Response will be defined as one of the following in either clinical exam, mammogram or US: Complete Response (CR)-Disappearance of all target lesions. Partial Response (PR)>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease-neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease <=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Pathologic Complete Response (pCR)
Időkeret: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery
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Pathologic Complete Response (pCR) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) and at surgery.
This will be defined as the number of patients that show a pCR after surgery.
pCR is defined as the absence of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.
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At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery
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Proliferation (Ki67) Measured at Baseline and After Completion of Study Treatment
Időkeret: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Correlation of proliferation (Ki67) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days).
Ki67 scoring was performed based on degree of staining (0= no staining, 1=weak nuclear staining, 2=moderate nuclear staining, 3=strong nuclear staining).
Ki67 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) Ki67 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
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At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Apoptosis (Cleaved Caspase-3) Measured at Baseline and After Completion of Study Treatment
Időkeret: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Apoptosis/cleaved caspase-3 (CC3) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days).
Scoring was based on the degree of staining (0=more than 90% of tumor cells with no staining, 1= more than 90% of tumor cells have weak staining, 2= more than 90% of tumor cells have moderate staining, 3= more than 90% of tumor cells have strong staining).
CC3 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) CC3 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
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At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Angiogenesis (vW, CD34) Markers as Measured at Baseline and After Completion of Study Treatment
Időkeret: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Angiogenesis (vW, CD34) markers will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days). Expressions were analyzed by light microscopy in invasive breast cancer regions. Tumor cells were assigned a score: 0 = no staining
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At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Epidermal Growth Factor Receptor (EGFR), and Matrix Metalloproteinases (MMPs), Measured at Baseline and After Completion of Study Treatment
Időkeret: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) with expressions analyzed by light microscopy in invasive breast cancer regions. MMP2 cytoplasmic staining intensity was assigned a score: 0=no reactivity,
Greater than or equal to 2+ score was considered positive for expression. EGFR membrane staining was assigned a score: 0 = no staining or faint staining in less than 10% of cells
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At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
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Side Effects From the Combination of Abraxane and Lapatinib
Időkeret: At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
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Side effects from the combination of Abraxane and Lapatinib will be assessed using CTCAE 3.0. Side effects that were related to study treatment and grade 3 or higher were collected where: Grade 1= Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life-threatening Grade 5 = Death |
At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
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Egyéb eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Circulating Tumor Cell Measurement
Időkeret: At baseline, then before each study treatment cycle begins (1 cycle = 21 days)
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Circulating tumor cell measurement will be assessed by lab tests done at baseline, then before each study treatment cycle begins (1 cycle = 21 days)
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At baseline, then before each study treatment cycle begins (1 cycle = 21 days)
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Együttműködők és nyomozók
Szponzor
Nyomozók
- Kutatásvezető: Virginia G. Kaklamani, MD, Northwestern University
Publikációk és hasznos linkek
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Becslés)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
- Bőrbetegségek
- Neoplazmák
- Neoplazmák webhelyenként
- Mellbetegségek
- Mellrák neoplazmák
- A farmakológiai hatás molekuláris mechanizmusai
- Enzim gátlók
- Antineoplasztikus szerek
- Tubulin modulátorok
- Antimitotikus szerek
- Mitózis modulátorok
- Daganatellenes szerek, fitogén
- Protein kináz inhibitorok
- Paclitaxel
- Albuminhoz kötött paklitaxel
- Lapatinib
Egyéb vizsgálati azonosító számok
- NU 05B2 (Egyéb azonosító: Northwestern University)
- STU00007257 (Egyéb azonosító: Northwestern University IRB)
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .
Klinikai vizsgálatok a Mellrák
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)Még nincs toborzásAnatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8 | Korai stádiumú emlőkarcinóma | Anatómiai Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8Egyesült Államok
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8Egyesült Államok
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Fred Hutchinson Cancer CenterMég nincs toborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8Egyesült Államok
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University of Southern CaliforniaNational Cancer Institute (NCI)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8 | Invazív emlőkarcinómaEgyesült Államok
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National Cancer Institute (NCI)Aktív, nem toborzóRosszindulatú szilárd daganat | Anatómiai Stage III Breast Cancer AJCC v8 | Anatómiai Stage IV Breast Cancer AJCC v8 | Invazív emlőkarcinóma | Mell adenokarcinómaEgyesült Államok
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City of Hope Medical CenterNational Cancer Institute (NCI)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8 | HER2-negatív emlőkarcinómaEgyesült Államok
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8Egyesült Államok
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); National Institute on Aging (NIA)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8Egyesült Államok
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Mayo ClinicNational Cancer Institute (NCI)ToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8Egyesült Államok
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Mayo ClinicToborzásAnatómiai stádiumú emlőrák AJCC v8 | Anatómiai Stage II Breast Cancer AJCC v8 | Anatómiai Stage III Breast Cancer AJCC v8 | Anatómiai Stage 0 Breast Cancer AJCC v8 | Hormonreceptor-pozitív emlőkarcinómaEgyesült Államok
Klinikai vizsgálatok a lapatinib ditosylate
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GlaxoSmithKlineBefejezve
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Institut Paoli-CalmettesFelfüggesztett
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German Breast GroupMegszűntÁttétes emlőrákNémetország
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R-PharmGlaxoSmithKlineMegszűntLokálisan előrehaladott vagy áttétes emlőrákEgyesült Államok, Olaszország, Ausztrália
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GlaxoSmithKlineVisszavontEgészséges alanyokEgyesült Államok
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GlaxoSmithKlineBefejezveNeoplazmák, mellEgyesült Államok, Koreai Köztársaság, Spanyolország
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University of Alabama at BirminghamGlaxoSmithKlineMegszűntPetefészekrákEgyesült Államok
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GlaxoSmithKlineBefejezveColorectalis rákEgyesült Államok, Kanada
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GlaxoSmithKlineMegszűntNeoplazmák, mellOlaszország, Egyesült Királyság
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Tragara Pharmaceuticals, Inc.Megszűnt