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

Study Overview
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Brief Summary
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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.

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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BIBF 1120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Age 18 years or older Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score <= 2 Patients must have given written informed consent (which must be consistent with ICH-GCP and local legislation) Exclusion Criteria: Time elapsed from last administration of BIBF 1120 in the previous trial to start of treatment in the present trial exceeds four weeks 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 Active ulcers (gastro-intestinal tract, skin) Major injuries and surgery within the past three weeks with incomplete wound healing Hypersensitivity to BIBF 1120 or the excipients of the trial drug Known secondary malignancy requiring therapy Active infectious disease Significant cardiovascular diseases (i.e. uncontrolled severe hypertension, unstable angina pectoris, history of myocardial infarction, congestive heart failure > NYHA II) Gastrointestinal disorders anticipated to interfere with the resorption of the study drug Brain metastases requiring therapy Absolute neutrophil count less than 1,500/mm3 Platelet count less than 100,000/mm3 Bilirubin greater than 1.5 mg/dl (> 26 µmol/L) 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) Serum creatinine greater than 2 mg/dl (> 176 µmol/L) Concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug Chemo-, radio-, or immunotherapy within the past four weeks prior to treatment with the trial drug Patients who are sexually active and unwilling to use a medically acceptable method of contraception Pregnancy or lactation 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) Patients unable to comply with the protocol Active alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BIBF 1120|nan|

What is the study measuring?
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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 |