advanced solid cancer

To evaluate maximum tolerated dose (MTD), safety, pharmacokinetics, pharmocodynamic, and anti-tumor activity of BI 836845

BI 836845

BI 836845

Concentrate for infusion

10

Primary objectives
Part I dose escalation study:
• To identify the MTD of BI 836845 therapy in patients with advanced solid cancers.
• To determine the Dose Limiting Toxicities (DLT).
• To evaluate the safety and tolerability profiles of BI 836845.
Part II expansion study:
• To evaluate anti-tumour activity in patients with metastatic or advanced solid tumours
at MTD and to further evaluate the safety profile and the pharmacokinetic (PK)
profile.
Secondary objectives
Part I and Part II study:
• To evaluate pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenomics
of BI 836845.

Patients must meet all of the following inclusion criteria to be eligible for participation in the
trial:
1. Patients with histologically or cytologically confirmed diagnosis of advanced, non
resectable and / or metastatic solid cancer, who have failed conventional treatment, or for
whom no therapy of proven efficacy exists, or who are not amenable to established forms
of treatment.
2. Patients should have evaluable disease, or at least one measurable lesion according to
RECIST criteria version 1.1 (R09-0262).
3. Age 18 years or older.
4. Life expectancy of at least 3 months in the opinion of the investigator.
5. Written informed consent that is consistent with ICH-GCP guidelines and local
legislation.
6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0, 1 or 2.
7. Patients must have recovered from any previous surgery and have had no major surgery
within the last 28 days prior to start of trial medication in the opinion of the investigator.
8. Cardiac left ventricular function with resting ejection fraction > 50% as determined by
ECHO or MUGA.
9. Absolute neutrophil count ≥ 1,500/µL.
10. Platelets ≥100,000/µL.
11. Total bilirubin ≤ 1.5x institution ULN.
12. AST and ALT ≤ 2.5x institution ULN (in case of hepatic primary cancer or known liver
metastases: AST and ALT ≤ 5x ULN).
13. Creatinine ≤1.5 x institution ULN.
14. Haemoglobin ≥ 9g/dL.
15. Haemoglobin A1c less than 8% and fasting plasma glucose ≤160 mg/dL (≤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.
17. Child-Pugh score 5 or 6. (this criterion is limited to HCC patients in Part II only).

Patients presenting with any of the following will be excluded from participation in the trial:
1. Active infectious disease considered by the investigator to be incompatible with the
protocol.
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 1 mg/day).
4. Patients not recovered from any therapy-related toxicities from previous chemo-,
hormone-, immuno-, molecular targeted, or radiotherapies to at least CTCAE ≤ 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, molecular-targeted therapy,
biological therapies (including trastuzumab), hormone therapy for breast cancer within 2
weeks of starting trial medication (excluding LHRH agonists in prostate cancer, or
bisphosphonates), or treatment with other investigational drugs.
7. Participation in another clinical trial within the past 4 weeks before start of trial
medication 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 IGF inhibitor.
12. Pregnancy or breast feeding.
13. Other malignancy requiring active therapy.
14. Patients with a history of diabetes mellitus.