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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00806819
First received: December 10, 2008
Last updated: November 14, 2014
Last verified: November 2014
  Purpose

The trial will be performed to evaluate if Nintedanib 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 Nintedanib/pemetrexed will be obtained.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Pemetrexed
Drug: Folic Acid
Drug: Nintedanib
Drug: Nintedanib plus pemetrexed
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Multicenter Phase III Trial of Nintedanib Plus Pemetrexed vs. Pemetrexed/ Placebo in Advanced or Recurrent Non Small Cell Lung Cancer Patients After Failure of First Line Therapy

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression Free Survival (PFS) as Assessed by Central Independent Review [ Time Frame: From randomisation until cut-off date 9 July 2012 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Overall Survival (Key Secondary Endpoint) [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]
    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.

  • Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]
    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.

  • Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]
    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.

  • Objective Tumor Response [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]
    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

  • Duration of Confirmed Objective Tumour Response [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    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.


  • Time to Confirmed Objective Tumour Response [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    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.


  • Disease Control [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    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.


  • Duration of Disease Control [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Tumour Size [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]
    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.

  • Clinical Improvement. [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    Clinical improvement was defined as the time from 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


  • Quality of Life (QoL) [ Time Frame: From randomisation until cut-off date 15 February 2013 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 718
Study Start Date: December 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nintedanib plus pemetrexed
Nintedanib along with standard therapy of pemetrexed
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.
Drug: Nintedanib Drug: Nintedanib plus pemetrexed
Active Comparator: Pemetrexed
Pemetrexed standard therapy
Drug: Pemetrexed
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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. 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 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 brain and 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 Nintedanib 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 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
  19. Active or chronic hepatitis C and/or B infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00806819

  Show 203 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00806819     History of Changes
Other Study ID Numbers: 1199.14, 2008-002072-10
Study First Received: December 10, 2008
Results First Received: November 14, 2014
Last Updated: November 14, 2014
Health Authority: Argentina: Ministry of Health
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Bosnia: Federal Ministry of Health
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Columbia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Ecuador: Public Health Ministry
Germany: Ministry of Health
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Korea: Food and Drug Administration
Latvia: State Agency of Medicines
Macedonia: Ministry of Health
Malaysia: Ministry of Health
Mexico: Ministry of Health
Moldova: Ministry of Health
Netherlands: Ministry of Health, Welfare and Sport
New Zealand: Medsafe
Panama: Commemorative Institute GORGAS of Studies of Health
Peru: Ministry of Health
Philippines: Department of Health
Poland: Ministry of Health
Romania: Ministry of Public Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Sweden: The National Board of Health and Welfare
Taiwan: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health
Ukraine: Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Nintedanib
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014