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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02763579




Registration number
NCT02763579
Ethics application status
Date submitted
4/05/2016
Date registered
5/05/2016
Date last updated
8/07/2020

Titles & IDs
Public title
A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
Scientific title
A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Secondary ID [1] 0 0
2015-004861-97
Secondary ID [2] 0 0
GO30081
Universal Trial Number (UTN)
Trial acronym
IMpower133
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Placebo

Experimental: Atezolizumab + Carboplatin + Etoposide - Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Active Comparator: Placebo + Carboplatin + Etoposide - Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.


Treatment: Drugs: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Treatment: Drugs: Carboplatin
Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Treatment: Drugs: Etoposide
Etoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Treatment: Drugs: Placebo
Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 - Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).
Timepoint [1] 0 0
Baseline until PD or death, whichever occurs first (up to approximately 23 months)
Primary outcome [2] 0 0
Duration of Overall Survival (OS)
Timepoint [2] 0 0
Baseline until death from any cause (up to approximately 23 months)
Secondary outcome [1] 0 0
Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1
Timepoint [1] 0 0
Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 46 months)
Secondary outcome [2] 0 0
Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
Timepoint [2] 0 0
First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 46 months)
Secondary outcome [3] 0 0
Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year
Timepoint [3] 0 0
6 months, 1 year (up to approximately 46 months)
Secondary outcome [4] 0 0
Percentage of Participants Alive at 1 Year and 2 Years
Timepoint [4] 0 0
1 year, 2 years (up to approximately 46 months)
Secondary outcome [5] 0 0
Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) Score
Timepoint [5] 0 0
Baseline until deterioration per symptom subscale (up to approximately 46 months)
Secondary outcome [6] 0 0
TTD Per EORTC QLQ Lung Cancer Module (LC13) Score
Timepoint [6] 0 0
Baseline until deterioration per symptom subscale (up to approximately 46 months)
Secondary outcome [7] 0 0
Percentage of Participants With Adverse Events
Timepoint [7] 0 0
Baseline until up to 90 days after end of treatment (up to approximately 46 months)
Secondary outcome [8] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)
Timepoint [8] 0 0
Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)
Secondary outcome [9] 0 0
Maximum Observed Serum Concentration (Cmax) of Atezolizumab - Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
Timepoint [9] 0 0
Predose (0 H) and postdose (0.5 H) on D1 of C1; predose (0 H) on D1 of C2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)
Secondary outcome [10] 0 0
Minimum Observed Serum Concentration (Cmin) of Atezolizumab - Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
Timepoint [10] 0 0
Predose (0 H) on D1 of C1, 2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)
Secondary outcome [11] 0 0
Plasma Concentration of Carboplatin
Timepoint [11] 0 0
Predose (0 H) and 5-10 minutes before end/1 H after end of carboplatin infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)
Secondary outcome [12] 0 0
Plasma Concentration of Etoposide
Timepoint [12] 0 0
Predose (0 H) and 5-10 minutes before end/1 H and 4H after end of etoposide infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration
Lung Study Group [VALG] staging system)

- No prior systemic treatment for ES-SCLC

- Eastern Cooperative Oncology Group performance status of 0 or 1

- Measurable disease, as defined by RECIST v1.1

- Adequate hematologic and end organ function

- Treatment-free for at least 6 months since last chemo/radiotherapy, among those
treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Active or untreated central nervous system (CNS) metastases as determined by computed
tomography (CT) or magnetic resonance imaging (MRI) evaluation

- Malignancies other than SCLC within 5 years prior to randomization, with the exception
of those with a negligible risk of metastasis or death treated with expected curative
outcome

- Pregnant or lactating women

- History of autoimmune disease

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is
permitted.

- Positive test result for human immunodeficiency virus (HIV)

- Active hepatitis B or hepatitis C

- Severe infections at the time of randomization

- Significant cardiovascular disease

- Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint
blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic
antibody

- History of severe (or known) hypersensitivity to chimeric or humanized antibodies or
fusion proteins or any component of atezolizumab formulation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
The Prince Charles Hospital; Oncology Dept. - Chermside
Recruitment hospital [3] 0 0
Royal Melbourne Hospital; Hematology and Medical Oncology - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
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United States of America
State/province [2] 0 0
Georgia
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Illinois
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Kentucky
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Maine
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United States of America
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Maryland
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Minnesota
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United States of America
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Nevada
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New Jersey
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New York
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North Carolina
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Tennessee
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Virginia
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Washington
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United States of America
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Wisconsin
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Wien
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Brazil
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BA
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Brazil
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RS
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Brazil
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SP
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Chile
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Recoleta
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Chile
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Santiago
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China
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Beijing
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China
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Changchun
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China
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Guangzhou
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China
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Harbin
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China
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Nanjing
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China
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Shanghai
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China
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Zhejiang
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China
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Zhengzhou
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Czechia
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Olomouc
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Czechia
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Praha 4 - Krc
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Czechia
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Praha 8
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Bordeaux
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France
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Caen
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France
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Lille
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France
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Marseille
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Germany
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Gauting
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Germany
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Großhansdorf
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Germany
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Halle
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Germany
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Heidelberg
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Immenhausen
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Greece
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Athens
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Patras
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Budapest
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Debrecen
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Seongnam-si
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Korea, Republic of
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Seoul
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Mexico
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Gdansk
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Otwock
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Poznan
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Warszawa
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Russian Federation
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Moskovskaja Oblast
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Russian Federation
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Moscow
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Russian Federation
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Novosibirsk
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Serbia
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Belgrade
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Serbia
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Nis
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Barcelona
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Madrid
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Malaga
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Sevilla
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Spain
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Zaragoza
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
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Exeter
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United Kingdom
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London
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United Kingdom
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was
designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1
[PD-L1] antibody) in combination with carboplatin plus (+) etoposide compared with treatment
with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC.
Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin +
etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the
induction phase followed by maintenance with atezolizumab or placebo until progressive
disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid
Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD
or symptomatic deterioration.
Trial website
https://clinicaltrials.gov/show/NCT02763579
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications