Phase I Trial of BI 836845 for Various Solid Cancer

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: BI 836845

Study type: Interventional

Funder types: Industry

Identifiers

NCT01403974

1280.1

Details and patient eligibility

About

This study is a phase I, open-label, dose escalation trial to determine the maximum tolerated dose (MTD) or the relevant biological dose (RBD) in the absence if a MTD of a new drug BI 836845 which blocks the insulin-like 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: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.
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) 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).
18. Patients eligible to undergo tumor biopsy should have normal coagulation parameters (INR and PTT within normal range). (this criterion is limited to patients in Part II only)

Exclusion criteria

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 (except tumor invading great vessel) 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. Use of any investigational drug within 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.
15. For patients that are to undergo tumor biopsy, a history of a hereditary bleeding disorder or clinically relevant major bleeding event in the past 6 months as judged by the investigator (this criterion is limited to patients in Part II only)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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61 participants in 16 patient groups

Part 1: 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, 8 and 15 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

Part 1: 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, 8 and 15 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

Part 1: 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, 8 and 15 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

Part 1: BI 836845 60 mg

Experimental group

Description:

Patients received 60 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 90 mg

Experimental group

Description:

Patients received 90 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 135 mg

Experimental group

Description:

Patients received 135 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 200 mg

Experimental group

Description:

Patients received 200 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 300 mg

Experimental group

Description:

Patients received 300 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 450 mg

Experimental group

Description:

Patients received 450 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 600 mg

Experimental group

Description:

Patients received 600 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 800 mg

Experimental group

Description:

Patients received 800 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 1050 mg

Experimental group

Description:

Patients received 1050 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: BI 836845 1400 mg

Experimental group

Description:

Patients received 1400 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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

Part 1: 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, 8 and 15 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

Part 2: Ewing's sarcoma family of tumours

Experimental group

Description:

Patients with Ewing's sarcoma family of tumours (ESFT) 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

Part 2: 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