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

Extension Study to Establish Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Patients With Previous Clinical Benefit From BIBF 1120

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BIBF 1120

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux cedex, France
    • 1199.16.3306A Boehringer Ingelheim Investigational Site
  • Clichy Cedex, France
    • 1199.16.3311A Boehringer Ingelheim Investigational Site
  • Clichy Cedex, France
    • 1199.16.3311B Boehringer Ingelheim Investigational Site
  • Paris, France
    • 1199.16.3312A Boehringer Ingelheim Investigational Site
  • Paris Cedex 10, France
    • 1199.16.3313A Boehringer Ingelheim Investigational Site
  • Paris Cedex 10, France
    • 1199.16.3313E Boehringer Ingelheim Investigational Site
  • Paris cedex 15, France
    • 1199.16.3302A Boehringer Ingelheim Investigational Site
• Germany
  • Freiburg/Breisgau, Germany
    • 1199.16.49001 Boehringer Ingelheim Investigational Site
  • Grosshansdorf, Germany
    • 1199.16.49004 Boehringer Ingelheim Investigational Site
  • Tübingen, Germany
    • 1199.16.49008 Boehringer Ingelheim Investigational Site
  • Wiesbaden, Germany
    • 1199.16.49005 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1	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).	From signing the informed consent until final follow-up, up to 991 days
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2	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).	From signing the informed consent until final follow-up, up to 991 days
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3	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).	From signing the informed consent until final follow-up, up to 991 days
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 4	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).	From signing the informed consent until final follow-up, up to 991 days
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 5	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).	From signing the informed consent until final follow-up, up to 991 days
Difference From Baseline for Liver Enzymes	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.	From signing the informed consent until end of treatment, up to 991 days
Difference From Baseline for Bilirubin, Creatinine and Glucose	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.	From signing the informed consent until end of treatment, up to 991 days
Difference From Baseline for Haemoglobin	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.	From baseline until end of treatment, up to 991 days
Difference From Baseline for Haematology and Differentials Parameters	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.	From signing the informed consent until end of treatment, up to 991 days
Difference From Baseline for Coagulation Parameters	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.	From signing the informed consent until end of treatment, up to 991 days
Difference From Baseline for Electrolytes	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.	From signing the informed consent until end of treatment, up to 991 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically Relevant Abnormalities for Vital Signs	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.	From baseline until final follow-up, up to 991 days
Pre-dose Concentration of Nintedanib in Plasma at Steady-state (Cpre,ss)	Cpre,ss represents the pre-dose concentration of Nintedanib in Plasma at steady-state at day 29	Just before drug administration every 28±7 days after day 29
Unconfirmed Best Overall Response	Unconfirmed best overall response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0). PD = Progressive disease.	Baseline until end of treatment, up to 991 days
Unconfirmed Best Objective Response	Unconfirmed best objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)	Baseline until end of treatment, up to 991 days
Clinical Benefit	Clinical benefit was defined as the absence of disease progression (no PD or nonevaluable clinically progressive disease) determined by RECIST (version 1.0).	Baseline until end of treatment, up to 991 days
Confirmed Objective Response	Confirmed objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)	Baseline until end of treatment, up to 991 days
Progression Free Survival	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.	First drug administration (in previous trial) until end of treatment, up to 1230 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: July 11, 2008
• First Submitted That Met QC Criteria: July 14, 2008
• First Posted (Estimate): July 15, 2008

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.16