Lume Lung 2 : BIBF 1120 Plus Pemetrexed Compared to Placebo Plus Pemetrexed in 2nd Line Nonsquamous NSCLC

NCT ID: NCT00806819

Last Updated: 2017-02-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

718 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2015-12-31

Brief Summary

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The trial will be performed to evaluate if BIBF 1120 in combination with standard pemetrexed therapy is more effective than placebo (inactive capsule) plus standard pemetrexed therapy in patients with stage IIIB, IV or recurrent NSCLC. Safety information about BIBF1120/pemetrexed will be obtained.

Detailed Description

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Conditions

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Carcinoma, Non-Small-Cell Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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nintedanib (BIBF1120) plus pemetrexed

nintedanib (BIBF1120) along with standard therapy of pemetrexed

Group Type EXPERIMENTAL

Nintedanib (BIBF1120)

Intervention Type DRUG

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

B12

Intervention Type DRUG

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

dexamethasone (or corticosteroid equivalent)

Intervention Type DRUG

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

Folic Acid

Intervention Type DRUG

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

Pemetrexed

Intervention Type DRUG

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Placebo plus pemetrexed

Pemetrexed standard therapy

Group Type PLACEBO_COMPARATOR

pemetrexed

Intervention Type DRUG

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

dexamethasone (or corticosteroid equivalent)

Intervention Type DRUG

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

B12

Intervention Type DRUG

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

placebo

Intervention Type DRUG

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Folic Acid

Intervention Type DRUG

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

nintedanib (BIBF1120) monotherapy

nintedanib (BIBF1120) monotherapy only for patients who discontinue pemetrexed

Group Type EXPERIMENTAL

Nintedanib (BIBF1120)

Intervention Type DRUG

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

pemetrexed monotherapy

pemetrexed monotherapy only for patients who discontinue nintedanib (BIBF1120) or placebo

Group Type ACTIVE_COMPARATOR

Pemetrexed

Intervention Type DRUG

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

B12

Intervention Type DRUG

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

dexamethasone (or corticosteroid equivalent)

Intervention Type DRUG

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

Folic Acid

Intervention Type DRUG

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

placebo monotherapy

placebo monotherapy only for patients who discontinue pemetrexed

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Interventions

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Nintedanib (BIBF1120)

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Intervention Type DRUG

Pemetrexed

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Intervention Type DRUG

pemetrexed

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Intervention Type DRUG

B12

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

Intervention Type DRUG

dexamethasone (or corticosteroid equivalent)

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

Intervention Type DRUG

placebo

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Intervention Type DRUG

dexamethasone (or corticosteroid equivalent)

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

Intervention Type DRUG

B12

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

Intervention Type DRUG

Folic Acid

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

Intervention Type DRUG

B12

1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed

Intervention Type DRUG

dexamethasone (or corticosteroid equivalent)

4 mg PO bid the day before, the day of and the day after each pemetrexed infusion

Intervention Type DRUG

Folic Acid

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

Intervention Type DRUG

placebo

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Intervention Type DRUG

Folic Acid

400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

Intervention Type DRUG

Nintedanib (BIBF1120)

starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.

Intervention Type DRUG

Pemetrexed

500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female patient aged 18 years or older.
2. Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or recurrent non small cell lung cancer (NSCLC) (non squamous histologies)
3. Relapse or failure of one first line chemotherapy (in the case of recurrent disease one additional prior regimen is allowed for adjuvant, neoadjuvant or neoadjuvant plus adjuvant therapy).
4. At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT.
5. Life expectancy of at least three months.
6. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
7. Patient has given written informed consent which must be consistent with the International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local legislation.

Exclusion Criteria

1. Previous therapy with other vascular endothelial growth factor (VEGF) inhibitors (other than bevacizumab) or pemetrexed for treatment of NSCLC
2. Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial
3. Chemotherapy, hormone therapy, immunotherapy with monoclonal antibodies, treatment with tyrosine kinase inhibitors, or radiotherapy (except for treatment of extremities) within the past four weeks prior to treatment with the trial drug, i.e., the minimum time elapsed since the last anticancer therapy and the first administration of BIBF 1120 must be four weeks
4. Inability to stop intake of NSAIDS (non steroidal anti inflammatory drugs) for several days
5. Active brain metastases (e.g. stable for \<4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants). Dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomisation)
6. Radiographic evidence of cavitary or necrotic tumors
7. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
8. History of clinically significant haemoptysis within the past 3 months
9. Therapeutic anticoagulation
10. History of major thrombotic or clinically relevant major bleeding event in the past 6 months
11. Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months,
12. Inadequate kidney, liver, blood clotting function
13. Inadequate blood count
14. Significant weight loss (\> 10 %) within the past 6 weeks prior to treatment in the present trial
15. Current peripheral neuropathy greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 except due to trauma
16. Pre-existing ascites (abdominal fluid collection) and/or clinically significant pleural effusion ( fluid collection between the lung and chest wall)
17. Major injuries and/or surgery within the past ten days prior to start of study drug
18. Incomplete wound healing
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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Boehringer Ingelheim Investigational Site

Downy, California, United States

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Fountain Valley, California, United States

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Fullerton, California, United States

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Long Beach, California, United States

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Meriden, Connecticut, United States

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Aventura, Florida, United States

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Boynton Beach, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Port Saint Lucie, Florida, United States

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Stuart, Florida, United States

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Galesburg, Illinois, United States

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Skokie, Illinois, United States

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Indianapolis, Indiana, United States

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New Albany, Indiana, United States

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Witchita, Kansas, United States

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Ashland, Kentucky, United States

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Louisville, Kentucky, United States

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Burlington, Massachusetts, United States

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Springfield, Massachusetts, United States

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Saint Louis Park, Minnesota, United States

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Grand Island, Nebraska, United States

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Farmington, New Mexico, United States

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Dunkirk, New York, United States

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Goshen, New York, United States

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Lake Success, New York, United States

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Nyack, New York, United States

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Asheville, North Carolina, United States

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Canton, Ohio, United States

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Sandusky, Ohio, United States

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Ephrata, Pennsylvania, United States

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Langhorne, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Germantown, Tennessee, United States

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Amarillo, Texas, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Bs. As. Codigo Buenos Aires, , Argentina

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Córdoba, , Argentina

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Pergamino, , Argentina

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Quilmes Buenos Aires, , Argentina

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Rosario, Santa Fe, , Argentina

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San Miguel de Tucumán, , Argentina

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Sydney, New South Wales, Australia

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Brisbane, Queensland, Australia

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Adelaide, South Australia, Australia

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Toorak Gardens, South Australia, Australia

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Melbourne, Victoria, Australia

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Perth, Western Australia, Australia

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Sydney, , Australia

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Banja Luka, , Bosnia and Herzegovina

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Sarajevo, , Bosnia and Herzegovina

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Belo Horizonte, , Brazil

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Belo Horizonte,Minas Gerais, , Brazil

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Cachoeira Do Itapemirim-ES, , Brazil

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Campinas SP, , Brazil

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Caxias do Sul, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Goiania Goias, , Brazil

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Ijuí, , Brazil

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Itajaí, , Brazil

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Jau/SP, , Brazil

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Londrina, Parana, , Brazil

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Pelotas Rio Grande Do Sul, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Salvador Bahia, , Brazil

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Santo André, , Brazil

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Sao Paulo - SP, , Brazil

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São Paulo, , Brazil

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Sorocaba Sao Paulo, , Brazil

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Thunder Bay, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Jardin Del Mar, Renaca, , Chile

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Las Condes, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Monteria, Cordoba, , Colombia

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Cuenca, , Ecuador

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Quito, , Ecuador

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Augsburg, , Germany

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Berlin, , Germany

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Gauting, , Germany

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Halle, , Germany

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Hemer, , Germany

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München, , Germany

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Hong Kong, , Hong Kong

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Deszk, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Dublin, , Ireland

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Daugavpils, , Latvia

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Liepāja, , Latvia

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Riga, , Latvia

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George Town, , Malaysia

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Kota Kinabalu, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuching, , Malaysia

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Chihuahua City, , Mexico

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Morelia, , Mexico

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Chisinau, , Moldova

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's-Hertogenbosch, , Netherlands

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Palmerston North, , New Zealand

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Wellington, , New Zealand

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Bitola, , North Macedonia

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Skopje, , North Macedonia

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Carrasquilla Panama, , Panama

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Panama City, , Panama

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Arequipa, , Peru

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Cercado Arequipa, , Peru

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Lima, , Peru

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Cebu, , Philippines

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Davao City, , Philippines

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Makati, , Philippines

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Quezon, , Philippines

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Olsztyn, , Poland

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Baia Mare, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Iași, , Romania

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Onești, , Romania

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Timișoara, , Romania

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Belgrade, , Serbia

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Kamenitz, , Serbia

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Niš, , Serbia

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Daegu, , South Korea

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Daejoen, , South Korea

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Gangdong-gu, Seoul, , South Korea

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Gyeonggi-do, , South Korea

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Jeonbuk, , South Korea

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Seochogu, Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Gävle, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Uppsala, , Sweden

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Aydin, , Turkey (Türkiye)

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Balcali-Adana, , Turkey (Türkiye)

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Diyarbakır, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Kocaeli, , Turkey (Türkiye)

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Chernihiv, , Ukraine

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Dnipropetrovks, , Ukraine

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Kharkiv, , Ukraine

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Uzhhorod, , Ukraine

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Boehringer Ingelheim Investigational Site

Vinnytsia, , Ukraine

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Countries

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United States Argentina Australia Bosnia and Herzegovina Brazil Canada Chile Colombia Ecuador Germany Hong Kong Hungary Ireland Latvia Malaysia Mexico Moldova Netherlands New Zealand North Macedonia Panama Peru Philippines Poland Romania Serbia South Korea Sweden Taiwan Thailand Turkey (Türkiye) Ukraine

References

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Lesaffre E, Edelman MJ, Hanna NH, Park K, Thatcher N, Willemsen S, Gaschler-Markefski B, Kaiser R, Manegold C. Statistical controversies in clinical research: futility analyses in oncology-lessons on potential pitfalls from a randomized controlled trial. Ann Oncol. 2017 Jul 1;28(7):1419-1426. doi: 10.1093/annonc/mdx042.

Reference Type DERIVED
PMID: 28184431 (View on PubMed)

Other Identifiers

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2008-002072-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1199.14

Identifier Type: -

Identifier Source: org_study_id

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