Carcinoma, Non-Small-Cell LungPhase 3NCT00806819

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

A Phase 3 study testing Nintedanib (BIBF1120), Pemetrexed and B12 in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 163 sites in 32 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Carcinoma, Non-Small-Cell Lung
What is being tested?: Nintedanib (BIBF1120), Pemetrexed and B12
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 718 participants
Where: 163 sitesin 32 countries
Study dates: Dec 2008to Dec 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female patient aged 18 years or older.
Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or recurrent non small cell lung cancer (NSCLC) (non squamous histologies)
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).
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.
Life expectancy of at least three months.
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
Patient has given written informed consent which must be consistent with the International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local legislation.

Who cannot join

Previous therapy with other vascular endothelial growth factor (VEGF) inhibitors (other than bevacizumab) or pemetrexed for treatment of NSCLC
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
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
Inability to stop intake of NSAIDS (non steroidal anti inflammatory drugs) for several days
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)
Radiographic evidence of cavitary or necrotic tumors

Show all 19Show fewer

Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
History of clinically significant haemoptysis within the past 3 months
Therapeutic anticoagulation
History of major thrombotic or clinically relevant major bleeding event in the past 6 months
Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months,
Inadequate kidney, liver, blood clotting function
Inadequate blood count
Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial
Current peripheral neuropathy greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 except due to trauma
Pre-existing ascites (abdominal fluid collection) and/or clinically significant pleural effusion ( fluid collection between the lung and chest wall)
Major injuries and/or surgery within the past ten days prior to start of study drug
Incomplete wound healing
Active or chronic hepatitis C and/or B infection Additional exclusion criteria apply

Trial locations and contacts

163 sites in 32 countries.

Country

City, postcode or hospital

163 sites in 32 countries

United States40 sites

Boehringer Ingelheim Investigational Site
Amarillo, Texas
Boehringer Ingelheim Investigational Site
Asheville, North Carolina
Boehringer Ingelheim Investigational Site
Ashland, Kentucky
Boehringer Ingelheim Investigational Site
Aventura, Florida
Boehringer Ingelheim Investigational Site
Boynton Beach, Florida
Boehringer Ingelheim Investigational Site
Burlington, Massachusetts
Boehringer Ingelheim Investigational Site
Canton, Ohio
Boehringer Ingelheim Investigational Site
Downy, California
Boehringer Ingelheim Investigational Site
Dunkirk, New York
Boehringer Ingelheim Investigational Site
Ephrata, Pennsylvania
Boehringer Ingelheim Investigational Site
Farmington, New Mexico
Boehringer Ingelheim Investigational Site
Fountain Valley, California
Boehringer Ingelheim Investigational Site
Fullerton, California
Boehringer Ingelheim Investigational Site
Galesburg, Illinois
Boehringer Ingelheim Investigational Site
Germantown, Tennessee
Boehringer Ingelheim Investigational Site
Goshen, New York
Boehringer Ingelheim Investigational Site
Grand Island, Nebraska
Boehringer Ingelheim Investigational Site
Indianapolis, Indiana
Boehringer Ingelheim Investigational Site
Jacksonville, Florida
Boehringer Ingelheim Investigational Site
Lake Success, New York
Boehringer Ingelheim Investigational Site
Langhorne, Pennsylvania
Boehringer Ingelheim Investigational Site
Long Beach, California
Boehringer Ingelheim Investigational Site
Louisville, Kentucky
Boehringer Ingelheim Investigational Site
Madison, Wisconsin
Boehringer Ingelheim Investigational Site
Meriden, Connecticut
Boehringer Ingelheim Investigational Site
Miami, Florida
Boehringer Ingelheim Investigational Site
Milwaukee, Wisconsin
Boehringer Ingelheim Investigational Site
New Albany, Indiana
Boehringer Ingelheim Investigational Site
New Port Richey, Florida
Boehringer Ingelheim Investigational Site
Nyack, New York
Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
Boehringer Ingelheim Investigational Site
Port Saint Lucie, Florida
Boehringer Ingelheim Investigational Site
Saint Louis Park, Minnesota
Boehringer Ingelheim Investigational Site
Sandusky, Ohio
Boehringer Ingelheim Investigational Site
Seattle, Washington
Boehringer Ingelheim Investigational Site
Skokie, Illinois
Boehringer Ingelheim Investigational Site
Spokane, Washington
Boehringer Ingelheim Investigational Site
Springfield, Massachusetts
Boehringer Ingelheim Investigational Site
Stuart, Florida
Boehringer Ingelheim Investigational Site
Witchita, Kansas

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Brazil20 sites

Boehringer Ingelheim Investigational Site
Belo Horizonte
Boehringer Ingelheim Investigational Site
Belo Horizonte,Minas Gerais
Boehringer Ingelheim Investigational Site
Cachoeira Do Itapemirim-ES
Boehringer Ingelheim Investigational Site
Campinas SP
Boehringer Ingelheim Investigational Site
Caxias do Sul
Boehringer Ingelheim Investigational Site
Curitiba
Boehringer Ingelheim Investigational Site
Florianópolis
Boehringer Ingelheim Investigational Site
Goiania Goias
Boehringer Ingelheim Investigational Site
Ijuí
Boehringer Ingelheim Investigational Site
Itajaí
Boehringer Ingelheim Investigational Site
Jau/SP
Boehringer Ingelheim Investigational Site
Londrina, Parana
Boehringer Ingelheim Investigational Site
Pelotas Rio Grande Do Sul
Boehringer Ingelheim Investigational Site
Porto Alegre
Boehringer Ingelheim Investigational Site
Rio de Janeiro
Boehringer Ingelheim Investigational Site
Salvador Bahia
Boehringer Ingelheim Investigational Site
Santo André
Boehringer Ingelheim Investigational Site
São Paulo
Boehringer Ingelheim Investigational Site
Sao Paulo - SP
Boehringer Ingelheim Investigational Site
Sorocaba Sao Paulo

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South Korea8 sites

Boehringer Ingelheim Investigational Site
Daegu
Boehringer Ingelheim Investigational Site
Daejoen
Boehringer Ingelheim Investigational Site
Gangdong-gu, Seoul
Boehringer Ingelheim Investigational Site
Gyeonggi-do
Boehringer Ingelheim Investigational Site
Jeonbuk
Boehringer Ingelheim Investigational Site
Seochogu, Seoul
Boehringer Ingelheim Investigational Site
Seoul
Boehringer Ingelheim Investigational Site
Suwon

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Australia7 sites

Boehringer Ingelheim Investigational Site
Adelaide, South Australia
Boehringer Ingelheim Investigational Site
Brisbane, Queensland
Boehringer Ingelheim Investigational Site
Melbourne, Victoria
Boehringer Ingelheim Investigational Site
Perth, Western Australia
Boehringer Ingelheim Investigational Site
Sydney, New South Wales
Boehringer Ingelheim Investigational Site
Sydney
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Toorak Gardens, South Australia

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Turkey (Türkiye)7 sites

Boehringer Ingelheim Investigational Site
Ankara
Boehringer Ingelheim Investigational Site
Antalya
Boehringer Ingelheim Investigational Site
Aydin
Boehringer Ingelheim Investigational Site
Balcali-Adana
Boehringer Ingelheim Investigational Site
Diyarbakır
Boehringer Ingelheim Investigational Site
Gaziantep
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Kocaeli

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Argentina6 sites

Boehringer Ingelheim Investigational Site
Bs. As. Codigo Buenos Aires
Boehringer Ingelheim Investigational Site
Córdoba
Boehringer Ingelheim Investigational Site
Pergamino
Boehringer Ingelheim Investigational Site
Quilmes Buenos Aires
Boehringer Ingelheim Investigational Site
Rosario, Santa Fe
Boehringer Ingelheim Investigational Site
San Miguel de Tucumán

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Germany6 sites

Boehringer Ingelheim Investigational Site
Augsburg
Boehringer Ingelheim Investigational Site
Berlin
Boehringer Ingelheim Investigational Site
Gauting
Boehringer Ingelheim Investigational Site
Halle
Boehringer Ingelheim Investigational Site
Hemer
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München

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Romania6 sites

Boehringer Ingelheim Investigational Site
Baia Mare
Boehringer Ingelheim Investigational Site
Bucharest
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Cluj-Napoca
Boehringer Ingelheim Investigational Site
Iași
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Onești
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Timișoara

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Ukraine5 sites

Boehringer Ingelheim Investigational Site
Chernihiv
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Dnipropetrovks
Boehringer Ingelheim Investigational Site
Kharkiv
Boehringer Ingelheim Investigational Site
Uzhhorod
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Vinnytsia

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Canada4 sites

Boehringer Ingelheim Investigational Site
Montreal, Quebec
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Québec, Quebec
Boehringer Ingelheim Investigational Site
Thunder Bay, Ontario
Boehringer Ingelheim Investigational Site
Toronto, Ontario

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Chile4 sites

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Jardin Del Mar, Renaca
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Las Condes
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Santiago
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Temuco

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Malaysia4 sites

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George Town
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Kota Kinabalu
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Kuala Lumpur
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Kuching

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New Zealand4 sites

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Auckland
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Christchurch
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Palmerston North
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Wellington

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Philippines4 sites

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Cebu
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Davao City
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Makati
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Quezon

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Sweden4 sites

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Gävle
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Stockholm
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Umeå
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Taiwan4 sites

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Kaohsiung City
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Taichung
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Tainan
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Hungary3 sites

Boehringer Ingelheim Investigational Site
Deszk
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Nyíregyháza
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Pécs

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Latvia3 sites

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Daugavpils
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Liepāja
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Peru3 sites

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Arequipa
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Serbia3 sites

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Belgrade
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Kamenitz
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Niš

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Bosnia and Herzegovina2 sites

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Banja Luka
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Sarajevo

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Ecuador2 sites

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Cuenca
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Quito

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Mexico2 sites

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Chihuahua City
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Morelia

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North Macedonia2 sites

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Bitola
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Panama2 sites

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Thailand2 sites

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Colombia1 site

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Hong Kong1 site

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Ireland1 site

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Moldova1 site

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Netherlands1 site

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Poland1 site

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About this study

Official title: Multicenter, Randomized, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Pemetrexed Therapy Compared to Placebo Plus Standard Pemetrexed Therapy in Patients With Stage IIIB/IV or Recurrent Non Small Cell Lung Cancer After Failure of First Line Chemotherapy

Conditions: Carcinoma, Non-Small-Cell Lung
Being tested: Nintedanib (BIBF1120), Pemetrexed, B12, dexamethasone (or corticosteroid equivalent), placebo
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nintedanib (BIBF1120)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.
PemetrexedDrug
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
pemetrexedDrug
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
B12Drug
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
dexamethasone (or corticosteroid equivalent)Drug
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
placeboDrug
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.
dexamethasone (or corticosteroid equivalent)Drug
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
B12Drug
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
Folic AcidDrug
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.
B12Drug
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
dexamethasone (or corticosteroid equivalent)Drug
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
Folic AcidDrug
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.
placeboDrug
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 AcidDrug
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)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.
PemetrexedDrug
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Study groups in NCT00806819
Study group	Role	What they receive
nintedanib (BIBF1120) plus pemetrexed	Experimental	nintedanib (BIBF1120) along with standard therapy of pemetrexed Receives: Drug: Nintedanib (BIBF1120); Drug: B12; Drug: dexamethasone (or corticosteroid equivalent); Drug: Folic Acid; Drug: Pemetrexed
Placebo plus pemetrexed	Placebo comparator	Pemetrexed standard therapy Receives: Drug: pemetrexed; Drug: dexamethasone (or corticosteroid equivalent); Drug: B12; Drug: placebo; Drug: Folic Acid
nintedanib (BIBF1120) monotherapy	Experimental	nintedanib (BIBF1120) monotherapy only for patients who discontinue pemetrexed Receives: Drug: Nintedanib (BIBF1120)
pemetrexed monotherapy	Active comparator	pemetrexed monotherapy only for patients who discontinue nintedanib (BIBF1120) or placebo Receives: Drug: Pemetrexed; Drug: B12; Drug: dexamethasone (or corticosteroid equivalent); Drug: Folic Acid
placebo monotherapy	Placebo comparator	placebo monotherapy only for patients who discontinue pemetrexed Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression Free Survival (PFS) as Assessed by Central Independent Review
Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria. Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).
Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until cut-off date 9 July 2012

Secondary outcomes (13)

Overall Survival (Key Secondary Endpoint)
Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Objective Tumor Response
Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0. This endpoint was analysed based on the central independent reviewer as well as the investigator
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Duration of Confirmed Objective Tumour Response
The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
This endpoint was analysed based on the central independent reviewer as well as the investigator.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Time to Confirmed Objective Tumour Response
Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
This endpoint was analysed based on the central independent reviewer as well as the investigator.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Disease Control
Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.
This endpoint was analysed based on the central independent reviewer as well as the investigator.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Duration of Disease Control
The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
This endpoint was analysed based on the central independent reviewer as well as the investigator.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Change From Baseline in Tumour Size
Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion. Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (adenocarcinoma vs. non-adenocarcinoma), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no) This endpoint was analysed based on the central independent reviewer as well as the investigator.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Clinical Improvement.
Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.
Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Quality of Life (QoL)
QoL was measured by standardised questionnaires (EQ-5D, EORTC QLQ-C30, EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items. The following were the main points of interest: Time to deterioration of cough (QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19). Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.
Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.
Measured: From randomisation until data cut-off (15 February 2013), Up to 30 months
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide
Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.
Measured: Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3
Incidence and Intensity of Adverse Events
Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.
Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.
Measured: From the first drug administration until 28 days after the last drug administration, up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2008Dec 2015

First posted11 Dec 2008 (estimated)
Study startDec 2008
Primary completionJun 2011
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 718 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00806819
Sponsor's protocol ID: 1199.14
Other IDs: 2008-002072-10, 2008
Status last verified: Dec 2016
First submitted: 10 Dec 2008
Last updated: 2 Feb 2017
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 28184431

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multicenter, Randomized, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Pemetrexed Therapy Compared to Placebo Plus Standard Pemetrexed Therapy in Patients With Stage IIIB/IV or Recurrent Non Small Cell Lung Cancer After Failure of First Line Chemotherapy
ClinicalTrials.gov ID: NCT00806819
Acronym / sponsor ID: 1199.14
Conditions: Carcinoma, Non-Small-Cell Lung
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 718 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Dec 2008
Primary completion: Jun 2011 (actual)
Study completion: Dec 2015 (actual)
First posted: 11 Dec 2008 (estimated)
Results: Posted 20 Nov 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 5

Arm	Type	Receives
nintedanib (BIBF1120) plus pemetrexed	Experimental	Drug: Nintedanib (BIBF1120), Drug: B12, Drug: dexamethasone (or corticosteroid equivalent), Drug: Folic Acid, Drug: Pemetrexednintedanib (BIBF1120) along with standard therapy of pemetrexed
Placebo plus pemetrexed	Placebo comparator	Drug: pemetrexed, Drug: dexamethasone (or corticosteroid equivalent), Drug: B12, Drug: placebo, Drug: Folic AcidPemetrexed standard therapy
nintedanib (BIBF1120) monotherapy	Experimental	Drug: Nintedanib (BIBF1120)nintedanib (BIBF1120) monotherapy only for patients who discontinue pemetrexed
pemetrexed monotherapy	Active comparator	Drug: Pemetrexed, Drug: B12, Drug: dexamethasone (or corticosteroid equivalent), Drug: Folic Acidpemetrexed monotherapy only for patients who discontinue nintedanib (BIBF1120) or placebo
placebo monotherapy	Placebo comparator	Drug: placeboplacebo monotherapy only for patients who discontinue pemetrexed

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female patient aged 18 years or older.
Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or recurrent non small cell lung cancer (NSCLC) (non squamous histologies)
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).
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.
Life expectancy of at least three months.

Key exclusion criteria (19 listed)

Previous therapy with other vascular endothelial growth factor (VEGF) inhibitors (other than bevacizumab) or pemetrexed for treatment of NSCLC
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
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
Inability to stop intake of NSAIDS (non steroidal anti inflammatory drugs) for several days
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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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.	Drug	nintedanib (BIBF1120) plus pemetrexed
Pemetrexed500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.	Drug	pemetrexed monotherapy
pemetrexed500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.	Drug	Placebo plus pemetrexed
B121000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed	Drug	pemetrexed monotherapy
dexamethasone (or corticosteroid equivalent)4 mg PO bid the day before, the day of and the day after each pemetrexed infusion	Drug	pemetrexed monotherapy
placebostarting 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.	Drug	placebo monotherapy
dexamethasone (or corticosteroid equivalent)4 mg PO bid the day before, the day of and the day after each pemetrexed infusion	Drug	Placebo plus pemetrexed
B121000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed	Drug	nintedanib (BIBF1120) plus pemetrexed
Folic Acid400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.	Drug	pemetrexed monotherapy
B121000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed	Drug	Placebo plus pemetrexed
dexamethasone (or corticosteroid equivalent)4 mg PO bid the day before, the day of and the day after each pemetrexed infusion	Drug	nintedanib (BIBF1120) plus pemetrexed
Folic Acid400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.	Drug	nintedanib (BIBF1120) plus pemetrexed
placebostarting 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.	Drug	Placebo plus pemetrexed
Folic Acid400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.	Drug	Placebo plus pemetrexed
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.	Drug	nintedanib (BIBF1120) monotherapy
Pemetrexed500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.	Drug	nintedanib (BIBF1120) plus pemetrexed

Primary outcome

Progression Free Survival (PFS) as Assessed by Central Independent Review
Time frame: From randomisation until cut-off date 9 July 2012
Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria. Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

13 secondary outcomes

Overall Survival (Key Secondary Endpoint)
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Objective Tumor Response
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Duration of Confirmed Objective Tumour Response
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Time to Confirmed Objective Tumour Response
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Disease Control
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Duration of Disease Control
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Change From Baseline in Tumour Size
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Clinical Improvement.
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Quality of Life (QoL)
Time frame: From randomisation until data cut-off (15 February 2013), Up to 30 months
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide
Time frame: Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3
Incidence and Intensity of Adverse Events
Time frame: From the first drug administration until 28 days after the last drug administration, up to 36 months

Results and safety

Results posted to the registry on 20 Nov 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nintedanib Plus Pemetrexed	353	7
Placebo Plus Pemetrexed	360	2

Primary outcome: Progression Free Survival (PFS) as Assessed by Central Independent Review

Time frame: From randomisation until cut-off date 9 July 2012. Median (Inter-Quartile Range). Unit: months

Measure	Nintedanib Plus Pemetrexed n = 353	Placebo Plus Pemetrexed n = 360
Value	4.4 (2.3 to 9.5)	3.6 (1.4 to 7.5)

Nintedanib Plus Pemetrexed vs Placebo Plus Pemetrexed: Hazard Ratio (HR): 0.83 (95% CI 0.70 to 0.99), p = 0.0435, Regression, Cox

Population analysed: RS

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first drug administration until 28 days after the last drug administration, up to 36 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nintedanib Plus Pemetrexed	104 of 347 (30%)	320 of 347 (92.2%)	Not reported
Placebo Plus Pemetrexed	117 of 357 (32.8%)	312 of 357 (87.4%)	Not reported

Limitations and caveats (from the sponsor): Recruitment for the study was stopped early based on the results of a pre defined futility analysis.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28184431Lesaffre 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.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

163 sites in 32 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nintedanib (BIBF1120), Pemetrexed and B12 in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 163 sites in 32 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 163 sites in United States, Brazil, South Korea, Australia, Turkey (Türkiye) and 27 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) as Assessed by Central Independent Review (time frame: From randomisation until cut-off date 9 July 2012). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00806819, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2017.