A Phase I Dose Escalation Trial of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours
1. Male or female patients with cytologically or histologically confirmed solid tumours
that are refractory to standard therapy or that have no standard therapy.
2. Patients should have evaluable disease, or at least one measurable lesion according
to Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1
3. Age, equal, or more than, 18 years old.
4. Life expectancy of at least 3 months.
5. Written informed consent that is consistent with ICH-GCP guidelines.
6. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
7. Patients must have recovered from any previous surgery and no major surgery within
the last 28 days prior to start of trial medication.
8. Cardiac left ventricular function with resting ejection fraction >50% as determined
by Echocardiography (ECHO) or Multiple Gated Acquisition scan (MUGA).
9. Absolute neutrophil count equal, or more than, 1,500/µl.
10. Platelets equal, or more than, 100,000/µl.
11. Total bilirubin equal, or less than 1.5 x institution upper limit of normal.
12. Aspartate Amino Transferas (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).
13. Creatinine equal, or less than, 1.5 x institution upper limit of normal.
14. Haemoglobin equal, or more than, 9g/dL.
15. Haemoglobin A1c less than 8% and fasting glucose, equal, or less than, 8.9 mmol/L (=
16. 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.
1. Active infectious disease.
2. Serious illness or concomitant non-oncological disease considered by the investigator
to be incompatible with the protocol.
3. History of thrombosis within 1 year of study or if concurrent anticoagulation
required, except low-dose warfarin (up to 1mg/day).
4. 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.
5. 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.
6. 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
7. Participation in another clinical trial within the past 4 weeks before start of
therapy or concomitantly with this trial.
8. Patients unable to comply with the protocol.
9. Active alcohol abuse or active drug abuse (at the discretion of the investigator).
10. Patients with unstable arrhythmias or unstable angina or severe obstructive pulmonary
disease within the last year.
11. For patients entering part II of the study, prior use of any insulin growth factor
12. Patients with a history of diabetes mellitus.
13. Pregnancy or breast feeding.