Dose Finding Study of BI 836880 in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is a Phase I, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously. The eligible patient population will be patients with advanced solid tumours. At any time during the trial, it will not be permitted to escalate to a dose which does not fulfil the escalation with overdose control (EWOC) criterion

Official Title
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A First-in Human Phase I, Non-randomised, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Repeated Intravenous Infusions in Patients With Solid Tumors.

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BI 836880


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age >= 18 years Histologically or cytologically confirmed malignancy which is locally advanced or metastatic solid tumor, and either refractory after standard therapy for the disease or for which standard therapy is not reliably effective, e.g. they do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD. ECOG performance status <= 2 Adequate hepatic, renal and bone marrow functions Signed written informed consent. Life expectancy min. 3 months in the opinion of the investigator Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade) sensory peripheral neuropathy CTCAE grade <= 2 or considered not clinically significant. adequate contraception by male and female patient during the trial and for at least 6 months after end of treatment. Exclusion criteria: Known hypersensitivity to the trial drugs or their excipients Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter of trial onset. Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period. patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 470 ms). QTcF will be calculated by Investigator as the mean of the 3 ECGs taken at screening. Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II). Uncontrolled hypertension defined as: blood pressure in rested and relaxed condition >=140 mmHg systolic, or >=90 mmHg diastolic (with or without medication), measured according to protocol. History of severe haemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator. Patient with brain metastases that are symptomatic and/or require therapy. Patients who require full-dose anticoagulation (according to local guidelines). Active alcohol or drug abuse in the opinion of the investigator. Patients who are under judicial protection and patients who are legally institutionalized. Patients unable or unwilling to comply with protocol Women who are pregnant, nursing, or who plan to become pregnant while in the trial

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 836880<br> | Drug: BI 836880<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint to assess the maximum tolerated dose (MTD) is based on the number of patients presenting dose-limiting toxicities (DLTs) using CTCAE v4.03, judged to be related to the study medication evaluated over the first cycle of treatment. |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing drug related AE leading to dose reduction or discontinuation from start of treatment until end of treatment |  | up to 24 weeks | 
| Exposure measures (AUC0-tz) after the first dose |  | 36 weeks | 
| Disposition kinetic measures (t1/2 ) after the first dose |  | 36 weeks |