CONTACT-01: Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
Study Details
Study Description
Brief Summary
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab given in combination with cabozantinib compared with docetaxel monotherapy in patients with metastatic NSCLC, with no sensitizing EGFR mutation or ALK translocation, who have progressed following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Atezolizumab + Cabozantinib Participants will receive atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on days 1-21 of each cycle. |
Drug: Cabozantinib
Cabozantinib will be administered orally, once daily at a dose of 40 mg on Days 1-21 of each cycle.
Drug: Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Other Names:
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Active Comparator: Docetaxel Participants will receive docetaxel on Day 1 of each 21-day cycle. |
Drug: Docetaxel
Docetaxel will be administered by IV infusion at a starting dose of 75mg/m2 on Day 1 of each 21-day cycle.
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Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Up to approximately 43 months]
Overall survival (OS) after randomization, defined as the time from randomization to death from any cause.
Secondary Outcome Measures
- PFS, as Determined by Investigator [Up to approximately 43 months]
PFS after randomization, defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).
- Confirmed Objective Response Rate (ORR), as Determined by Investigator [Up to approximately 43 months]
Confirmed objective response rate (ORR), defined as the proportion of participants with a complete or partial response on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.
- Duration of response (DOR), as Determined by Investigator [Up to approximately 43 months]
Duration of response (DOR) for participants with confirmed ORR, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).
- Time to Confirmed Deterioration in Patient-Reported Physical Functioning (PF) [Up to approximately 43 months]
Time to confirmed deterioration in patient-reported physical functioning (PF) as measured by the corresponding scores from the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30).
- Time to Confirmed Deterioration in Patient-Reported Global Health Status (GHS) [Up to approximately 43 months]
Time to confirmed deterioration in patient-reported Global Health Status (GHS) as measured by the corresponding scores from the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30).
- PFS Rates Assessed by Investigator [6 months and 1 year]
- OS Rates [1 and 2 years]
- Percentage of Participants With Adverse Events [Up to approximately 43 months]
- Minimum Serum Concentration (Cmin) of Atezolizumab [Predose and postdose on Day 1 of Cycle 1; and Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)]
- Maximum Serum Concentration (Cmax) of Atezolizumab [Predose and postdose on Day 1 of Cycle 1; and Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)]
- Minimum Serum Concentration (Cmin) of Cabozantinib [Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)]
- Maximum Serum Concentration (Cmax) of Cabozantinib [Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)]
- Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [Predose on Day 1 of Cycle 1 (each cycle is 21 days)]
- Number of ADAs to Atezolizumab After Treatment [Predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 (each cycle is 21 days)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed metastatic NSCLC
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Documented radiographic disease progression during or following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially for metastatic NSCLC
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Measurable disease per RECIST v1.1 outside CNS as assessed by investigator
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Known PD-L1 status or availability of tumor tissue for central PD-L1 testing
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ECOG Performance Status score of 0 or 1
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Recovery to baseline or Grade <=1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable on supportive therapy in the opinion of the investigator
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Adequate hematologic and end-organ function
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Negative HIV test at screening
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Negative hepatitis B surface antigen (HBsAg) test at screening
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Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
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Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
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For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs,
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For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
Exclusion Criteria:
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Prior therapy with the following agents for NSCLC: Cabozantinib, Docetaxel, Combination of an anti-PD-L1/PD-1 antibody concurrently with a vascular endothelial growth factor (VEGF)R targeting tyrosine kinase inhibitor (TKI)
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Treatment with investigational therapy within 28 days prior to initiation of study treatment
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Documentation of known sensitizing mutation in the EGFR gene or ALK fusion oncogene
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Patients with known ROS1 rearrangements, BRAF V600E mutations, or other actionable oncogenes with approved therapies if available
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Symptomatic, untreated, or actively progressing CNS metastases
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History of leptomeningeal disease
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Uncontrolled tumor-related pain
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Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more frequently than once monthly)
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Severe hepatic impairment
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Uncontrolled or symptomatic hypercalcemia
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Any other active malignancy at the time of initiation of study treatment or diagnosis of another malignancy within 3 years prior to initiation of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, incidental prostate cancer, or carcinoma in situ of the prostate, cervix, or breast
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Stroke, transient ischemic attack, myocardial infarction or other symptomatic ischemic events within 6 months of initiation of study treatment
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Significant vascular disease within 6 months of initiation of study treatment
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Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
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Active tuberculosis
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Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion on the investigator, could impact patient safety
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Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
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Current treatment with anti-viral therapy for HBV
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Major surgical procedure, other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
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Pregnant or lactating females, or intention of becoming pregnant during the treatment with atezolizumab in combination with cabozantinib in the experimental arm or during the treatment with docetaxel in the control arm, or within 5 months after the final dose of atezolizumab and/or 4 months after the final dose of cabozantinib, whichever is later.
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Ongoing Grade >= 2 sensory or motor neuropathy
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Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions: Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: Rash must cover < 10% of body surface area.
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Pharmacologically uncompensated, symptomatic hypothyroidism
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History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
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Prior allogeneic stem cell or solid organ transplantation
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Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
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Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
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Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor confirmation has been obtained. Patients who received mineralocorticoids, inhaled or low-dose systemic corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
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History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
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Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
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Known allergy or hypersensitivity to any component of the cabozantinib formulation
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History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80
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Concomitant anticoagulation with coumarin agents, direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
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History of risk factors for torsades de pointes
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Corrected QT interval corrected through use of Fridericia's formula (QTcF) > 480 ms per ECG within 14 days before initiation of study treatment
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Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal antihypertensive treatment
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Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
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Abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess within 6 months before initiation of study treatment
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Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation
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Lesions invading major pulmonary blood vessels
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Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, coagulopathy, or other history of significant bleeding within 3 months before initiation of study treatment
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Serious non-healing wound/ulcer/bone fracture
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Malabsorption syndrome
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Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption are also excluded.
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Requirement for hemodialysis or peritoneal dialysis
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Inability to swallow tablets
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Stanford University | Palo Alto | California | United States | 94305 |
2 | Kaiser Permanente - San Diego | San Diego | California | United States | 92120 |
3 | Sansum Clinic | Santa Barbara | California | United States | 93105 |
4 | Rocky Mountain Cancer Centers | Denver | Colorado | United States | 80220 |
5 | Regional Cancer Care Associates | Bethesda | Maryland | United States | 20817 |
6 | Karmanos Cancer Center | Detroit | Michigan | United States | 48201 |
7 | Minnesota Oncology Hematology | Saint Paul | Minnesota | United States | 55102 |
8 | Oncology Associates of Oregon, P.C | Eugene | Oregon | United States | 97401 |
9 | Consultants in Medical Oncology and Hematology | Broomall | Pennsylvania | United States | 19008 |
10 | Charleston Oncology, P .A | Charleston | South Carolina | United States | 29414 |
11 | Texas Oncology - Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
12 | Huntsman Cancer Institute at The University of Utah | Salt Lake City | Utah | United States | 84112 |
13 | Virginia Cancer Specialists (Fairfax) - USOR | Fairfax | Virginia | United States | 22031 |
14 | Oncology and Hematology Associates of Southwest Virginia, Inc.,-Blacksburg | Roanoke | Virginia | United States | 24014 |
15 | Royal North Shore Hospital; Oncology | St. Leonards | New South Wales | Australia | 2065 |
16 | Townsville Hospital | Townsville | Queensland | Australia | 4810 |
17 | Flinders Medical Centre | Bedford Park | South Australia | Australia | 5042 |
18 | Austin Hospital Olivia Newton John Cancer Centre | Heidelberg | Victoria | Australia | 3084 |
19 | Affinity Oncology | Nedlands | Western Australia | Australia | 6009 |
20 | LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie | Graz | Austria | 8036 | |
21 | Ordensklinikum Linz Elisabethinen | Linz | Austria | 4020 | |
22 | Lhk Feldkirch; Interne Medizin Abt. | Rankweil | Austria | 6830 | |
23 | Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt. | Salzburg | Austria | 5020 | |
24 | Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie | Wien | Austria | 1090 | |
25 | Institut Jules Bordet | Anderlecht | Belgium | 1070 | |
26 | Cliniques Universitaires St-Luc | Bruxelles | Belgium | 1200 | |
27 | UZ Gent | Gent | Belgium | 9000 | |
28 | Clinique Ste-Elisabeth | Namur | Belgium | 5000 | |
29 | Clinique de l'Europe | Amiens | France | 80090 | |
30 | CHU Angers,Service de Pneumologie | Angers | France | 49933 | |
31 | CHU de Grenoble | Grenoble | France | 38043 | |
32 | Hopital Dupuytren; Pneumologie | Limoges | France | 87042 | |
33 | Hôpital Saint Joseph; Oncologie Medicale | Marseille | France | 13285 | |
34 | Centre Regional de Lutte contre le Cancer Val d Aurelle - Paul Lamarque; Service d oncologie | Montpellier | France | 34298 | |
35 | Centre Hospitalier de Mulhouse - Hopital Emile Muller | Mulhouse | France | 68070 | |
36 | Hopital Tenon;Pneumologie | Paris | France | 75970 | |
37 | Zentralklinik Bad Berka GmbH; Pneumologie | Bad Berka | Germany | 99437 | |
38 | Kliniken Essen Mitte Evang. Huyssens Stiftung/Knappschaft GmbH | Essen | Germany | 45136 | |
39 | Universitaetsklinikum Giessen und Marburg GmbH; Medizinische Klinik IV und V | Gießen | Germany | 35392 | |
40 | KRH Klinikum Siloah-Oststadt-Heidehaus | Hannover | Germany | 30459 | |
41 | Klinikum Koeln-Merheim; Lungenklinik | Köln | Germany | 51109 | |
42 | Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik | Mainz | Germany | 55131 | |
43 | Universitaetsklinikum Giessen und Marburg | Marburg | Germany | 35043 | |
44 | Brüderkrankenhaus St. Josef Paderborn | Paderborn | Germany | 33098 | |
45 | Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine | Athens | Greece | 115 22 | |
46 | Henri Dunant Hospital; Oncology Dept. | Athens | Greece | 115 26 | |
47 | Uoa Sotiria Hospital; Oncology | Athens | Greece | 115 27 | |
48 | Univ General Hosp Heraklion; Medical Oncology | Heraklion | Greece | 711 10 | |
49 | Euromedical General Clinic of Thessaloniki; Oncology Department | Thessaloniki | Greece | 546 45 | |
50 | AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico | Napoli | Campania | Italy | 80131 |
51 | Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica | Bologna | Emilia-Romagna | Italy | 40138 |
52 | Azienda Ospedaliero Universitaria di Parma | Parma | Emilia-Romagna | Italy | 43126 |
53 | Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica | Ravenna | Emilia-Romagna | Italy | 48100 |
54 | Irccs Centro Di Riferimento Oncologico (CRO) | Aviano | Friuli-Venezia Giulia | Italy | 33081 |
55 | Azienda Ospedaliera San Camillo Forlanini | Roma | Lazio | Italy | 00152 |
56 | Policlinico Umberto I, Oncologia B | Roma | Lazio | Italy | 00161 |
57 | IRCCS AOU San Martino - IST | Genova | Liguria | Italy | 16132 |
58 | ASST Spedali Civili di Brescia | Brescia | Lombardia | Italy | 25123 |
59 | Instituto Europeo di Oncologia | Milan | Lombardia | Italy | 20141 |
60 | Istituto Clinico Humanitas | Rozzano (MI) | Lombardia | Italy | 20089 |
61 | Ospedale Vito Fazzi | Lecce | Puglia | Italy | 73100 |
62 | A.O.U Careggi | Florence | Toscana | Italy | 50124 |
63 | Hyogo Cancer Center | Hyogo | Japan | 673-0021 | |
64 | Sendai Kousei Hospital | Miyagi | Japan | 980-0873 | |
65 | Osaka International Cancer Institute | Osaka | Japan | 541-8567 | |
66 | National Cancer Center Hospital | Tokyo | Japan | 104-0045 | |
67 | The Cancer Institute Hospital of JFCR | Tokyo | Japan | 135-8550 | |
68 | Chungbuk National University Hospital | Cheongju-si | Korea, Republic of | 28644 | |
69 | National Cancer Center | Goyang-si | Korea, Republic of | 10408 | |
70 | St. Vincent's Hospital | Gyeonggi-do | Korea, Republic of | 16247 | |
71 | Ajou University Medical Center | Gyeonggi-do | Korea, Republic of | 16499 | |
72 | Samsung Changwon Hospital | Gyeongsangnam-do | Korea, Republic of | 51353 | |
73 | Gachon University Gil Medical Center | Incheon | Korea, Republic of | 21565 | |
74 | Seoul National University Bundang Hospital | Seongnam-si | Korea, Republic of | 13605 | |
75 | Korea University Anam Hospital | Seoul | Korea, Republic of | 02841 | |
76 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | 03722 | |
77 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
78 | Seoul St Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
79 | Ulsan University Hosiptal | Ulsan | Korea, Republic of | 44033 | |
80 | Centrum Onkologii im. Prof. Franciszka Łukaszczyka; Ambulatorium Chemioterapii | Bydgoszcz | Poland | 85-796 | |
81 | SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej | Bytom | Poland | 41-902 | |
82 | Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter. | Gliwice | Poland | 44-101 | |
83 | Szpital Wojewódzki im. Mikołaja Kopernika; Oddział Dzienny Chemioterapii | Koszalin | Poland | 75-581 | |
84 | Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii | Otwock | Poland | 05-400 | |
85 | Hospital Pulido Valente; Servico de Pneumologia | Lisboa | Portugal | 1796-001 | |
86 | Centro Hospitalar do Porto - Hospital de Santo António; Oncologia | Porto | Portugal | 4099-001 | |
87 | Hospital CUF Porto; Servico Pneumologia | Porto | Portugal | 4100-180 | |
88 | IPO do Porto; Servico de Oncologia Medica | Porto | Portugal | 4200-072 | |
89 | CHVNG/E_Unidade 1; Servico de Pneumologia | Vila Nova de Gaia | Portugal | 4434-502 | |
90 | Regional Clinical Oncology Hospital | Yaroslavl | Jaroslavl | Russian Federation | 150054 |
91 | MEDSI Clinical Hospital on Pyatnitsky Highway; Department of antitumor drug therapy | Moscow | Moskovskaja Oblast | Russian Federation | 143422 |
92 | S-Pb clinical scientific practical center of specialized kinds of medical care (oncological) | Saint-Petersburg | Russian Federation | 197758 | |
93 | GBUZ Leningradskaya state clinical hospital | St. Petersburg | Russian Federation | 194291 | |
94 | Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia | A Coruña | LA Coruña | Spain | 15006 |
95 | Vall d´Hebron Institute of Oncology (VHIO), Barcelona | Barcelona | Spain | 08035 | |
96 | Institut Catala d Oncologia Hospital Duran i Reynals | Barcelona | Spain | 08908 | |
97 | Hospital Universitario La Paz; Servicio de Oncologia | Madrid | Spain | 28046 | |
98 | Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia | Sevilla | Spain | 41014 | |
99 | Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia | Valencia | Spain | 46015 | |
100 | Hospital Universitari i Politecnic La Fe; Oncologia | Valencia | Spain | 46026 | |
101 | Addenbrookes Hospital | Cambridge | United Kingdom | CB2 0QQ | |
102 | Beatson West of Scotland Cancer Centre | Glasgow | United Kingdom | G12 0YN | |
103 | Huddersfield Royal Infirmary; The Learning Centre | Huddersfield | United Kingdom | HD3 3EA | |
104 | Barts & London School of Med; Medical Oncology | London | United Kingdom | EC1A 7BE | |
105 | University College London Hospital | London | United Kingdom | NW1 - 2PG | |
106 | Royal Free Hospital | London | United Kingdom | NW3 2QS | |
107 | Chelsea & Westminster Hospital | London | United Kingdom | SW10 9NH |
Sponsors and Collaborators
- Hoffmann-La Roche
- Exelixis
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- GO41892