BIBW 2992 (Afatinib) and Vinorelbine in Japanese Patients With Advanced Solid Tumours

Study Overview
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Brief Summary
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To identify the Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine i.v. by assessment of Dose Limiting Toxicities (DLT); To assess safety and anti-tumour efficacy and determine pharmacokinetic characteristics of afatinib and vinorelbine i.v.

Official Title
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An Open-label Phase I Study of Once Daily Oral Treatment With BIBW 2992 in Combination With Weekly Vinorelbine Intravenous Injection in Japanese Patients With Advanced Solid Tumours

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: afatinib 20mg
* Drug: afatinib 40mg
* Drug: vinorelbine IV 25 or 20mg/m2


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed diagnosis of malignancy that is advanced and for which standard therapies do not exist or are no longer effective. Life expectancy at least 12 weeks Eastern Cooperative Oncology Group Performance Status 0 or 1 Adequate hepatic, renal, haematologic and other organ function Written informed consent Exclusion criteria: Chemotherapy, immunotherapy, surgery and radiotherapy within the past 4 weeks Prior treatment with afatinib and or vinorelbine Clinically significant active infectious disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: afatinib and vinorelbine IV<br>patient to receive 20mg or 40mg of po daily afatinib in combination with vinorelbine IV | Drug: afatinib 20mg<br>* patient to receive afatinib low dose po daily in combination with vinorelbine iv<br>Drug: afatinib 40mg<br>* patient to receive afatinib high dose po daily in combination with vinorelbine iv<br>Drug: vinorelbine IV 25 or 20mg/m2<br>* patient to receive standard dose vinorelbine once a week for four times per cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Dose Limiting Toxicities (DLTs) During 1st Course | DLTs and Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine iv. (MTD = not determined) | during 1st course | 
| Drug-related Adverse Events | Number of patients with drug-related adverse events | during the treatment period or up to 28 days after the completion of drug administration, up to 730 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss for Afatinib | area under the plasma concentration-time curve following dose at steady state over the dosing interval τ | pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as with Vinorelbine) and 20th dose (as without Vinorelbine) | 
| Cmax,ss for Afatinib | maximum measured plasma concentration at steady state | pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as with Vinorelbine) and 20th dose (as without Vinorelbine) | 
| AUC0-∞ for Vinorelbine | area under the blood concentration-time curve of the analyte over the time interval from 0 extrapolated to infinity | predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as with afatinib) and 1st dose (as without afatinib) | 
| Cmax for Vinorelbine | maximum measured blood concentration | predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as with afatinib) and 1st dose (as without afatinib) | 
| Objective Tumour Response | According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and assessed by CT or MRI: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Pre-treatment, every 8 weeks after start of study treatment, end of treatment |