Phase I Trial of BI 836845 for Various Solid Cancer

NCT01403974 | Completed Phase 1 Results

• 1 other identifier: 1280.1
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Part 1: Maximum Tolerated Dose (MTD) of BI 836845 During the First Treatment Course of the Dose Escalation Phase.

  In the absence of MTD, the relevant biological dose (RBD) of BI 836845 during the first treatment course of the dose escalation phase was reported. The MTD was defined as the highest dose level of BI 836845 at which no more than 1 out of 6 patients experienced a drug related dose limiting toxicity (DLT) during the first course of treatment. Starting dose of 10 milligrams (mg) BI 836845, administered thrice every 3 weeks. Dose levels evaluated were: 10 mg, 20 mg, 40 mg, 60 mg, 90 mg, 135 mg, 200 mg, 300 mg, 450 mg, 600 mg, 800 mg, 1050 mg, 1400 mg and 1800 mg. The BI 836845 dose which could achieve a plateau in total Insulin-like growth factor 1 (IGF-1) plasma concentrations was considered the RBD.

  During the first course of treatment, up to 21 days

• Part 1: Number of Patients With Dose Limiting Toxicities (DLTs) During the Maximum Tolerated Dose (MTD) Evaluation Period

  Number of participants with DLTs occurring during the first treatment course of the dose escalation part. DLT was defined as drug-related adverse events meeting the criteria summarized below: * Common terminology criteria for adverse events (CTCAE) grade 4 neutropenia for ≥ 7 days (d) * Febrile neutropenia with single temperature of \> 38.3°C/ ≥ 38°C more than 1 hour (h) * Documented infection with high neutrophile count * CTCAE grade 4 thrombocytopenia/CTCAE grade 3 thrombocytopenia associated with bleeding requiring transfusion * AST (Aspartate Amino Transferase)/ALT (Alanine Amino Transferase) \> 5x normal * CTCAE grade 3/4 non-hematologic toxicity * CTCAE grade ≥2 infusion reaction * CTCAE grade ≥2 nausea and/or vomiting for ≥7 d * CTCAE grade ≥3 skin toxicity * CTCAE grade ≥3 hyperglycemia * Any electrolyte grade 3 AE * No recovery from non-DLT CTCAE grade \>2 * Sustained fatigue/asthenia grade 3 for longer than 96 h * Other event qualified as DLT by the investigator

  During the first course of treatment, up to 21 days

Secondary Outcomes (9)

• Objective Tumour Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1

  First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

• Duration of Objective Response

  First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

• Best Overall Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Criteria Version 1.1

  First treatment administration until disease progression or last evaluable assessment in absence of progression; Up to 72 weeks

• Disease Control

  First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

• Part 2 - Biopsiable Tumours: Progression-free Survival (PFS)

  First treatment administration until tumour progression or death. Up to 72 weeks

Study Arms (16)

Part 1: BI 836845 10 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 20 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 40 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 60 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 90 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 135 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 200 mg

EXPERIMENTAL

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

Drug: BI 836845

Part 1: BI 836845 300 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 450 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 600 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 800 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 1050 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 1400 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 1: BI 836845 1800 mg

EXPERIMENTAL

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.

Drug: BI 836845

Part 2: Ewing's sarcoma family of tumours

EXPERIMENTAL

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.

Drug: BI 836845

Part 2: Biopsiable tumours

EXPERIMENTAL

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.

Drug: BI 836845

Interventions

BI 836845 DRUG

Intravenous infusion once every week

Also known as: Xentuzumab

Part 1: BI 836845 10 mg; Part 1: BI 836845 1050 mg; Part 1: BI 836845 135 mg; Part 1: BI 836845 1400 mg; Part 1: BI 836845 1800 mg; Part 1: BI 836845 20 mg; Part 1: BI 836845 200 mg; Part 1: BI 836845 300 mg; Part 1: BI 836845 40 mg; Part 1: BI 836845 450 mg; Part 1: BI 836845 60 mg; Part 1: BI 836845 600 mg; Part 1: BI 836845 800 mg; Part 1: BI 836845 90 mg; Part 2: Biopsiable tumours; Part 2: Ewing's sarcoma family of tumours

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients should have evaluable disease, or at least one measurable lesion according to RECIST criteria version 1.1.
• Age 18 years or older.
• Life expectancy of at least 3 months in the opinion of the investigator.
• Written informed consent that is consistent with ICH-GCP guidelines and local legislation.
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
• 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.
• Cardiac left ventricular function with resting ejection fraction \> 50% as determined by ECHO or MUGA.
• Absolute neutrophil count = 1,500/µL.
• Platelets =100,000/µL.
• Total bilirubin = 1.5x institution ULN.
• AST and ALT = 2.5x institution ULN (in case of hepatic primary cancer or known liver metastases: AST and ALT = 5x ULN).
• Creatinine =1.5 x institution ULN.
• Haemoglobin = 9g/dL.
• Haemoglobin A1c less than 8% and fasting plasma glucose =160 mg/dL (=8.9 mmol/L).

You may not qualify if:

• Active infectious disease considered by the investigator to be incompatible with the protocol.
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
• 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).
• 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.
• 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, 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.
• Use of any investigational drug within 4 weeks before start of trial medication 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 IGF inhibitor.
• Pregnancy or breast feeding.
• Other malignancy requiring active therapy.
• Patients with a history of diabetes mellitus.
• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

China Medical University Hospital

Taichung, 404, Taiwan

Location

NCKUH

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (1)

• de Bono J, Lin CC, Chen LT, Corral J, Michalarea V, Rihawi K, Ong M, Lee JH, Hsu CH, Yang JC, Shiah HS, Yen CJ, Anthoney A, Jove M, Buschke S, Fuertig R, Schmid U, Goeldner RG, Strelkowa N, Huang DC, Bogenrieder T, Twelves C, Cheng AL. Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours. Br J Cancer. 2020 Apr;122(9):1324-1332. doi: 10.1038/s41416-020-0774-1. Epub 2020 Mar 12.

  PMID: 32161368 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Interventions

xentuzumab

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 was conducted in a sequential manner and Part 2 was conducted in a parallel design.

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 27, 2011
• Study Start: July 19, 2011
• Primary Completion: July 8, 2015
• Study Completion: December 23, 2015
• Last Updated: July 25, 2025
• Results First Posted: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (3)