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A Phase I/II Open Label Extension Study of BIBF 1120 Administered Orally Once or Twice Daily to Establish Safety, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and Clinical Benefit From Previous Therapy With BIBF 1120

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00715403
First received: July 11, 2008
Last updated: November 24, 2014
Last verified: November 2014
  Purpose

The primary objective of this trial is to evaluate the long-term safety of BIBF 1120 in terms of incidence and intensity of Adverse Events and changes in safety laboratory parameters.

Secondary objectives are the collection of further safety data (vital signs), efficacy data and the determination of pharmacokinetic characteristics during long-term therapy with BIBF 1120.


Condition Intervention Phase
Neoplasms
Drug: BIBF 1120
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Extension Study to Establish Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Patients With Previous Clinical Benefit From BIBF 1120

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 [ Time Frame: From signing the informed consent until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    All patients who had grade 1 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 [ Time Frame: From signing the informed consent until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    All patients who had grade 2 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 [ Time Frame: From signing the informed consent until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    All patients who had grade 3 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Incidence and Intensity of Adverse Events With Highest CTCAE Grade 4 [ Time Frame: From signing the informed consent until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    All patients who had grade 4 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Incidence and Intensity of Adverse Events With Highest CTCAE Grade 5 [ Time Frame: From signing the informed consent until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    All patients who had grade 5 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Difference From Baseline for Liver Enzymes [ Time Frame: From signing the informed consent until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

  • Difference From Baseline for Bilirubin, Creatinine and Glucose [ Time Frame: From signing the informed consent until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

  • Difference From Baseline for Haemoglobin [ Time Frame: From baseline until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline for Haemoglobin (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

  • Difference From Baseline for Haematology and Differentials Parameters [ Time Frame: From signing the informed consent until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

  • Difference From Baseline for Coagulation Parameters [ Time Frame: From signing the informed consent until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline (normalized value) in coagulation parameters Prothrombin time, international normalised ratio (PT-INR) and partial thromboplastin time. Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

  • Difference From Baseline for Electrolytes [ Time Frame: From signing the informed consent until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.


Secondary Outcome Measures:
  • Clinically Relevant Abnormalities for Vital Signs [ Time Frame: From baseline until final follow-up, up to 991 days ] [ Designated as safety issue: No ]
    Clinically relevant abnormalities for Vital Signs (systolic blood pressure, diastolic blood pressure, and pulse rate). New abnormal findings or worsening of baseline conditions were reported as Adverse Events.

  • Pre-dose Concentration of Nintedanib in Plasma at Steady-state (Cpre,ss) [ Time Frame: Just before drug administration every 28±7 days after day 29 ] [ Designated as safety issue: No ]
    Cpre,ss represents the pre-dose concentration of Nintedanib in Plasma at steady-state at day 29

  • Unconfirmed Best Overall Response [ Time Frame: Baseline until end of treatment, up to 991 days ] [ Designated as safety issue: No ]

    Unconfirmed best overall response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0).

    PD = Progressive disease.


  • Unconfirmed Best Objective Response [ Time Frame: Baseline until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Unconfirmed best objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)

  • Clinical Benefit [ Time Frame: Baseline until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Clinical benefit was defined as the absence of disease progression (no PD or nonevaluable clinically progressive disease) determined by RECIST (version 1.0).

  • Confirmed Objective Response [ Time Frame: Baseline until end of treatment, up to 991 days ] [ Designated as safety issue: No ]
    Confirmed objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)

  • Progression Free Survival [ Time Frame: First drug administration (in previous trial) until end of treatment, up to 1230 days ] [ Designated as safety issue: No ]

    Percentage of participants that experienced progression free survival (PFS), assessed by RECIST (Response Evaluation Criteria In Solid Tumours) (version 1.0), by day 1230. Progression was defined as progressive disease (PD) or non-evaluable clinically progressive disease.

    PFS was defined for patients without PD at screening as the time from first treatment with the trial drug in the previous trial until onset of PD or death, whatever comes earlier.

    Patients with PD could enter the trial if they showed signs of clinical benefit. For patients with PD at screening, the RECIST assessment at screening was used as a new baseline value and PFS was the time from first treatment with the trial drug in this trial until the onset of progressive disease in this trial or death, whatever comes first.



Enrollment: 41
Study Start Date: October 2004
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients with advanced solid tumours who have completed a previous study with BIBF 1120. The patients should not have progression of their underlying tumour disease unless there is evidence for significant clinical benefit (e.g. symptom improvement) from treatment with BIBF 1120.
  2. Age 18 years or older
  3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score <= 2
  4. Patients must have given written informed consent (which must be consistent with ICH-GCP and local legislation)

Exclusion Criteria:

  1. Time elapsed from last administration of BIBF 1120 in the previous trial to start of treatment in the present trial exceeds four weeks
  2. Presence of drug related toxicity > grade 2 CTC from previous therapy with BIBF 1120 or presence of drug related continuous toxicity of grade 2 for seven or more consecutive days which would preclude ongoing chronic therapy with BIBF 1120
  3. Active ulcers (gastro-intestinal tract, skin)
  4. Major injuries and surgery within the past three weeks with incomplete wound healing
  5. Hypersensitivity to BIBF 1120 or the excipients of the trial drug
  6. Known secondary malignancy requiring therapy
  7. Active infectious disease
  8. Significant cardiovascular diseases (i.e. uncontrolled severe hypertension, unstable angina pectoris, history of myocardial infarction, congestive heart failure > NYHA II)
  9. Gastrointestinal disorders anticipated to interfere with the resorption of the study drug
  10. Brain metastases requiring therapy
  11. Absolute neutrophil count less than 1,500/mm3
  12. Platelet count less than 100,000/mm3
  13. Bilirubin greater than 1.5 mg/dl (> 26 µmol/L)
  14. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
  15. Serum creatinine greater than 2 mg/dl (> 176 µmol/L)
  16. Concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug
  17. Chemo-, radio-, or immunotherapy within the past four weeks prior to treatment with the trial drug
  18. Patients who are sexually active and unwilling to use a medically acceptable method of contraception
  19. Pregnancy or lactation
  20. Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy (visit 2) or concomitantly with this trial (except for a previous study with BIBF 1120)
  21. Patients unable to comply with the protocol
  22. Active alcohol or drug abuse
  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: NCT00715403

Locations
France
1199.16.3306A Boehringer Ingelheim Investigational Site
Bordeaux cedex, France
1199.16.3311A Boehringer Ingelheim Investigational Site
Clichy Cedex, France
1199.16.3311B Boehringer Ingelheim Investigational Site
Clichy Cedex, France
1199.16.3313A Boehringer Ingelheim Investigational Site
Paris Cedex 10, France
1199.16.3313E Boehringer Ingelheim Investigational Site
Paris Cedex 10, France
1199.16.3302A Boehringer Ingelheim Investigational Site
Paris cedex 15, France
1199.16.3312A Boehringer Ingelheim Investigational Site
Paris, France
Germany
1199.16.49001 Boehringer Ingelheim Investigational Site
Freiburg/Breisgau, Germany
1199.16.49004 Boehringer Ingelheim Investigational Site
Grosshansdorf, Germany
1199.16.49008 Boehringer Ingelheim Investigational Site
Tübingen, Germany
1199.16.49005 Boehringer Ingelheim Investigational Site
Wiesbaden, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00715403     History of Changes
Other Study ID Numbers: 1199.16 
Study First Received: July 11, 2008
Results First Received: November 14, 2014
Last Updated: November 24, 2014
Health Authority: France: AFFSAPS
Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:
Nintedanib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016