Durvalumab With Stereotactic Body Radiation Therapy (SBRT) vs Placebo With SBRT in Early Stage Unresected Non-small Cell Lung Cancer (NSCLC) Patients/ Osimertinib Following SBRT in Patients With Early Stage Unresected NSCLC Harboring an EGFR Mutation

NCT ID: NCT03833154

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

724 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-06

Study Completion Date

2028-04-04

Brief Summary

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This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.

An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.

Detailed Description

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Patients with Stage I/II lymph node negative NSCLC and confirmed to meet all eligibility criteria will be randomized 1:1 to receive either Durvalumab + SoC SBRT or placebo + SoC SBRT.

The primary objective of main cohort is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of Overall Survival (OS).

In addition, a study cohort with a sufficient number of patients harboring an EGFR-TKI sensitizing mutation, will receive Osimertinib treatment after completion of SoC SBRT as definitive treatment of Stage I/II lymph node-negative NSCLC. The primary objective of Osimertinib cohort is to assess efficacy of Osimertinib following SoC SBRT in terms of 4-year PFS. Key secondary objectives include safety, OS and efficacy of Osimertininb treatment with SBRT.

Conditions

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Carcinoma, Non-Small-Cell Lung

Keywords

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NSCLC Early-Stage NSCLC Lung cancer Double- Blind PD-L1 MEDI4736 Durvalumab Osimertinib PFS OS Unresected lung cancer Medically Inoperable Operable with Patient refusal SBRT SABR EGFR

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double- Blind

Study Groups

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SoC SBRT + Durvalumab Therapy (Main Cohort)

SBRT

Durvalumab (PD-L1 monoclonal antibody) 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.

SoC SBRT + Placebo Therapy (Main Cohort)

SBRT

Placebo (matching placebo for infusion) every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo for infusion every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.

SoC SBRT + Osimertinib Therapy (Osimertinib cohort, single-arm, open-label separate cohort)

SBRT

Osimertinib 80mg every day \[qd\] for oral administration up to 36 months or until progression. Osimertinib treatment should start within 7 to 14 days after completion of SBRT

Group Type EXPERIMENTAL

(Osimertinib cohort, single-arm, open-label separate cohort)

Intervention Type DRUG

Osimertinib 80 mg every day \[qd\] orally for up to 36 months or until progression or other discontinuation criteria are met. Osimertinib treatment should start from 7 to 14 days after completion of SBRT

Interventions

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Durvalumab

Durvalumab 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.

Intervention Type DRUG

Placebo

Matching placebo for infusion every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.

Intervention Type OTHER

(Osimertinib cohort, single-arm, open-label separate cohort)

Osimertinib 80 mg every day \[qd\] orally for up to 36 months or until progression or other discontinuation criteria are met. Osimertinib treatment should start from 7 to 14 days after completion of SBRT

Intervention Type DRUG

Other Intervention Names

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MEDI4736

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years
2. Planned SoC SBRT as definitive treatment
3. World Health Organization (WHO)/ECOG PS of 0, 1 or 2
4. Life expectancy of at least 12 weeks
5. Body weight \>30 kg
6. Submission of tumor tissue sample if available
7. Adequate organ and marrow function required
8. Patients with central or peripheral lesions are eligible
9. Staging studies must be done during screening (PET-CT within 10 weeks)
10. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions


1. Age ≥18 years
2. Planned SoC SBRT as definitive treatment
3. WHO/ECOG PS of 0, 1, or 2
4. Patients with central or peripheral lesions are eligible
5. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
6. Staging studies must be done during screening (PET-CT within 10 weeks)
7. Submission of tumor tissue sample if available
8. Confirmation by local laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
9. Adequate bone marrow reserve or organ function required
10. Female patients should be using highly effective contraceptive measures
11. Male patients should be asked to use barrier contraceptives (ie, condoms) during sex with all partners during the trial and avoid procreation

Exclusion Criteria

1. Mixed small cell and non-small cell cancer
2. History of allogeneic organ transplantation
3. History of another primary malignancy with exceptions
4. History of active primary immunodeficiency
5. Epidermal growth factor receptor local testing is strongly recommended prior to enrollment. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
6. Prior exposure to immune-mediated therapy with exceptions


1. Mixed small cell and non-small cell cancer
2. Patients with known or increased risk factor for QTc prolongation
3. Treatment with any of the following:

* Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
* Prior treatment with neoadjuvant or adjuvant EGFR TKI
* Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4
4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
5. Any of the following cardiac criteria

* Mean resting corrected QT interval \>470 msec, obtained from 3 ECGs
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval
* Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Tuscaloosa, Alabama, United States

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Chandler, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Duarte, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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Newark, Delaware, United States

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Washington D.C., District of Columbia, United States

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Bay Pines, Florida, United States

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Jacksonville, Florida, United States

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Miami Beach, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Decatur, Illinois, United States

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Elmhurst, Illinois, United States

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Naperville, Illinois, United States

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Fort Wayne, Indiana, United States

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Cedar Rapids, Iowa, United States

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Iowa City, Iowa, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Metairie, Louisiana, United States

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New Orleans, Louisiana, United States

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South Portland, Maine, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Rosedale, Maryland, United States

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Silver Spring, Maryland, United States

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Towson, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Royal Oak, Michigan, United States

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Duluth, Minnesota, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Lebanon, New Hampshire, United States

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Camden, New Jersey, United States

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Paramus, New Jersey, United States

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Albany, New York, United States

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East Syracuse, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Stony Brook, New York, United States

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Syracuse, New York, United States

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The Bronx, New York, United States

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The Bronx, New York, United States

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Winston-Salem, North Carolina, United States

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Grand Forks, North Dakota, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Sioux Falls, South Dakota, United States

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Watertown, South Dakota, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Sherman, Texas, United States

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Burlington, Vermont, United States

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Richmond, Virginia, United States

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Bellingham, Washington, United States

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Seattle, Washington, United States

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Spokane Valley, Washington, United States

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Milwaukee, Wisconsin, United States

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Clayton, , Australia

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Aalst, , Belgium

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Charleroi, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Barretos, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Volta Redonda, , Brazil

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Edmonton, Alberta, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Fuzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hefei, , China

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Jinan, , China

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Nanjing, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Wuhan, , China

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Zhengzhou, , China

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Bron, , France

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Dijon, , France

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Lyon, , France

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Nantes, , France

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Pierre-Bénite, , France

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Toulouse, , France

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Villejuif, , France

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Dresden, , Germany

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Göttingen, , Germany

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Halle, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Homburg, , Germany

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Regensburg, , Germany

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Trier, , Germany

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Athens, , Greece

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Athens, , Greece

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Thessaloniki, , Greece

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Florence, , Italy

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Genova, , Italy

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Padua, , Italy

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Fukuoka, , Japan

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Hiroshima, , Japan

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Kobe, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Sakaishi, , Japan

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Sapporo, , Japan

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Sunto-gun, , Japan

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Toyoake-shi, , Japan

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Yokohama, , Japan

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Utrecht, , Netherlands

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Bydgoszcz, , Poland

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Elblag, , Poland

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Gdansk, , Poland

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Katowice, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Hato Rey, , Puerto Rico

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Kazan, Tatarstan, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Ufa, , Russia

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Yekaterinburg, , Russia

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Cheongju-si, , South Korea

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Goyang-si, , South Korea

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Gyeonggi-do, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Badajoz, , Spain

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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San Sebastián, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kocaeli, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada China France Germany Greece Israel Italy Japan Netherlands Poland Puerto Rico Russia South Korea Spain Turkey (Türkiye) United Kingdom

Related Links

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https://www.lungcancerstudylocator.com/trial/listing/193775

Lung Cancer Study Locator details (for US)

Other Identifiers

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2018-002572-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9103C00001

Identifier Type: -

Identifier Source: org_study_id