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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: BI 836845

Study type: Interventional

Funder types: Industry

Identifiers

NCT01317420

2010-021714-29 (EudraCT Number)

1280.2

Details and patient eligibility

About

This study is a phase I, open-label, dose escalation trial to determine the maximum tolerated dose (MTD) of a new drug BI 836845 which blocks the insulin growth factor (IGF) pathway believed to be involved in cancer growth. BI 836845 will be administered for the very first time into cancer patients.

The study will also look at the overall safety of the drug, and examine the drug levels in the body at specific timepoints during the trial (pharmacokinetic profile); the effect the drug may have on tumours will also be examined (pharmacodynamics).

Enrollment: 64 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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 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).
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 (= 160 mg/dL).
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. 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.
18. 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

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.
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 investigational drugs.
7. Use of any investigational drug within 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 (IGF) inhibitor.
12. Patients with a history of diabetes mellitus.
13. Pregnancy or breast feeding.
14. Patients that are to undergo biopsy should not have a history of a hereditary bleeding disorder as judged by the investigator.
15. Patients that are to undergo biopsy should pause acetylsalicylic acid treatment for at least 7 days prior to biopsy tissue collection.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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64 participants in 13 patient groups

BI 836845 10 mg

Experimental group

Description:

Patients received 10 milligram (mg) of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 20 mg

Experimental group

Description:

Patients received 20 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 40 mg

Experimental group

Description:

Patients received 40 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 80 mg

Experimental group

Description:

Patients received 80 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 160 mg

Experimental group

Description:

Patients received 160 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 320 mg

Experimental group

Description:

Patients received 320 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 640 mg

Experimental group

Description:

Patients received 640 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 1280 mg

Experimental group

Description:

Patients received 1280 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 1800 mg

Experimental group

Description:

Patients received 1800 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 2400 mg

Experimental group

Description:

Patients received 2400 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

BI 836845 3600 mg

Experimental group

Description:

Patients received 3600 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Treatment:

Drug: BI 836845

Ewings sarcoma

Experimental group

Description:

Patients with Ewing's family of tumours (EFT) or primitive neuroectodermal tumour (PNET) receiving relevant biological dose (RBD) of BI 836845 1000 mg, administered in each course of 21 days by a 1-hour infusion at the start of each week in expansion part of the study.

Treatment:

Drug: BI 836845

Biopsiable tumours

Experimental group

Description:

Patients with all solid tumour types who had tumours suitable for biopsy receiving relevant biological dose (RBD) of BI 836845 1000 mg, administered in each course of 21 days by a 1-hour infusion at the start of each week in expansion part of the study.

Treatment:

Drug: BI 836845