Trial to Determine MTD of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours and Later a Weekly Dosing Schedule in Selected Tumour Types

Inclusion criteria

• Male or female patients with cytologically or histologically confirmed solid tumours that are refractory to standard therapy or that have no standard therapy.
• Patients should have evaluable disease, or at least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1
• Age, equal, or more than, 18 years old.
• Life expectancy of at least 3 months.
• Written informed consent that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
• Patients must have recovered from any previous surgery and no major surgery within the last 28 days prior to start of trial medication.
• Cardiac left ventricular function with resting ejection fraction >50% as determined by Echocardiography (ECHO) or Multiple Gated Acquisition scan (MUGA).
• Absolute neutrophil count equal, or more than, 1,500/µl.
• Platelets equal, or more than, 100,000/µl.
• Total bilirubin equal, or less than 1.5 x institution upper limit of normal.
• Aspartate Amino Transferase (AST) (Serum glutamic oxaloacetic transaminase (SGOT)) / Alanine Amino Transferase (ALT) (Serum glutamic pyruvic transaminase (SGPT )) equal, or less than, 2.5 x upper limit of normal (in case of known liver metastases AST and/or ALT, equal, or less than, 5 x upper limit of normal).
• Creatinine equal, or less than, 1.5 x institution upper limit of normal.
• Haemoglobin equal, or more than, 9g/dL.
• Haemoglobin A1c less than 8% and fasting glucose, equal, or less than, 8.9 mmol/L (= 160 mg/dL).
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment.
• Patients entering part II of the study should have cytologically or histologically confirmed disease from the Ewing's family of tumours/PNET (cohort 1), or solid tumours suitable for biopsy (cohort 2), that are refractory to standard therapy or that have no standard therapy.
• Patients eligible to undergo biopsy should have normal coagulation parameters (INR and PTT within normal ranges) and platelet count (equal, or more than, 100,000/µl) prior to biopsy tissue collection.

Exclusion criteria

• Active infectious disease.
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
• History of thrombosis within 1 year of study or if concurrent anticoagulation required.
• Patients not recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, molecular targeted, or radiotherapies to at least Common Terminology Criteria for Adverse Events (CTCAE) equal, or less than, Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to first trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
• Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least 4 weeks before starting trial medication, no history of cerebral oedema or bleeding in the past 4 weeks before starting trial medication and must be on a stable or reducing dose of dexamethasone. Anti-epileptic therapy will be allowed if the patient is stable on antiepileptic treatment for 4 weeks, or more, without adjustments before starting trial medication.
• Patients who have been treated with any of the following within 4 weeks of starting trial medication: chemotherapy, immunotherapy, radiotherapy, biological therapies (including trastuzumab), molecular targeted, hormone therapy for breast cancer within 2 weeks of starting trial medication (excluding Luteinizing-hormone-releasing hormone (LHRH) agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
• Use of any investigational drug within 4 weeks before start of therapy or concomitantly with this trial.
• Patients unable to comply with the protocol.
• Active alcohol abuse or active drug abuse (at the discretion of the investigator).
• Patients with unstable arrhythmias or unstable angina or severe obstructive pulmonary disease within the last year.
• For patients entering part II of the study, prior use of any insulin growth factor (IGF) inhibitor.
• Patients with a history of diabetes mellitus.
• Pregnancy or breast feeding.
• Patients that are to undergo biopsy should not have a history of a hereditary bleeding disorder as judged by the investigator.
• Patients that are to undergo biopsy should pause acetylsalicylic acid treatment for at least 7 days prior to biopsy tissue collection.