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

NCT01317420 | Completed Phase 1 Results

• 2 other identifiers: 1280.22010-021714-29
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) or Relevant Biological Dose (RBD) of BI 836845 During the First Treatment Course of the Dose Escalation Phase

  To determine the MTD or relevant biological dose (RBD) of BI 836845 during the first treatment course of the dose escalation phase. The MTD was defined as the highest dose level of BI 836845 below the maximum dose administered at which no more than 1 out of 6 patients experienced a drug-related DLT during the first course of treatment. Starting dose of 10 mg BI 836845, administered once every 3 weeks. Dose levels evaluated were: 10 mg, 20 mg, 40 mg, 80 mg, 160 mg, 320 mg, 640 mg, 1280 mg, 1800 mg, 2400 mg, and 3600 mg. In the absence of the MTD, the RBD, where a plateau in total Insulin-like growth factor 1 (IGF-1) level and total neutralisation of IGF activity is predicted, is reported.

  During the first course of treatment, up to 21 days

• Percentage of Patients With Dose Limiting Toxicities (DLTs) During the First Treatment Course of the Dose Escalation Phase

  DLTs defined as drug related: CTCAE Grade 4 neutropenia lasting ≥7 days; febrile neutropenia and/or documented infection with Absolute Neutrophil Count \<1.0x109/L; Grade 4 thrombocytopaenia or Grade 3 associated with bleeding needing platelet transfusion; Grade ≥3 increased hepatic enzymes; Grade 3 or 4 non-haematologic toxicity with exceptions; Grade ≥2 infusion reaction despite adequate pre-medication; Grade ≥2 nausea and/or vomiting persisting for ≥7 days despite antiemetic treatment; Grade ≥3 skin toxicity despite adequate supportive care measures for up to 2 weeks if it does not reach an improvement to grade ≤2; Grade ≥3 hyperglycaemia resistant to treatment with anti-diabetic agents; any electrolyte grade 3 AE refractory to optimal correction therapy; no recovery from a non-DLT grade \>2 toxicity to grade 1 within 14 days of administered dose; sustained fatigue/asthenia grade 3 for \>96 h associated with deterioration of Performance score (Eastern Cooperative Oncology Group).

  During the first course of treatment, up to 21 days

Secondary Outcomes (9)

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

  First treatment administration, up to 246 days.

• Objective Tumour Response

  First treatment administration, up to 246 days.

• Duration of Objective Response

  First treatment administration, up to 246 days.

• Disease Control

  First treatment administration, up to 246 days.

• Progression-free Survival (PFS)

  First treatment administration until tumour progression or death, up to 162 days.

Study Arms (13)

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 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Drug: BI 836845

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 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Drug: BI 836845

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 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Drug: BI 836845

BI 836845 80 mg

EXPERIMENTAL

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

Drug: BI 836845

BI 836845 160 mg

EXPERIMENTAL

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

Drug: BI 836845

BI 836845 320 mg

EXPERIMENTAL

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

Drug: BI 836845

BI 836845 640 mg

EXPERIMENTAL

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

Drug: BI 836845

BI 836845 1280 mg

EXPERIMENTAL

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

Drug: BI 836845

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 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study

Drug: BI 836845

BI 836845 2400 mg

EXPERIMENTAL

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

Drug: BI 836845

BI 836845 3600 mg

EXPERIMENTAL

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

Drug: BI 836845

Ewings sarcoma

EXPERIMENTAL

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.

Drug: BI 836845

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

Also known as: Xentuzumab

BI 836845 10 mg; BI 836845 1280 mg; BI 836845 160 mg; BI 836845 1800 mg; BI 836845 20 mg; BI 836845 2400 mg; BI 836845 320 mg; BI 836845 3600 mg; BI 836845 40 mg; BI 836845 640 mg; BI 836845 80 mg; Biopsiable tumours; Ewings sarcoma

Eligibility Criteria

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

You may qualify if:

• Male or female patients with cytologically or histologically confirmed solid tumours that are refractory to standard therapy or that have no standard therapy.
• Patients should have evaluable disease, or at least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1
• Age, equal, or more than, 18 years old.
• Life expectancy of at least 3 months.
• Written informed consent that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
• Patients must have recovered from any previous surgery and no major surgery within the last 28 days prior to start of trial medication.
• Cardiac left ventricular function with resting ejection fraction \>50% as determined by Echocardiography (ECHO) or Multiple Gated Acquisition scan (MUGA).
• Absolute neutrophil count equal, or more than, 1,500/µl.
• Platelets equal, or more than, 100,000/µl.
• Total bilirubin equal, or less than 1.5 x institution upper limit of normal.
• 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).
• Creatinine equal, or less than, 1.5 x institution upper limit of normal.
• Haemoglobin equal, or more than, 9g/dL.
• Haemoglobin A1c less than 8% and fasting glucose, equal, or less than, 8.9 mmol/L (= 160 mg/dL).

You may not qualify if:

• Active infectious disease.
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
• History of thrombosis within 1 year of study or if concurrent anticoagulation required.
• 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.
• 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, 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.
• Use of any investigational drug within 4 weeks before start of therapy 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 insulin growth factor (IGF) inhibitor.
• Patients with a history of diabetes mellitus.
• Pregnancy or breast feeding.
• Patients that are to undergo biopsy should not have a history of a hereditary bleeding disorder as judged by the investigator.
• Patients that are to undergo biopsy should pause acetylsalicylic acid treatment for at least 7 days prior to biopsy tissue collection.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

The Royal Marsden Hospital, Sutton

Sutton, SM2 5PT, United Kingdom

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 17, 2011
• Study Start: April 13, 2011
• Primary Completion: February 15, 2016
• Study Completion: February 15, 2016
• Last Updated: July 11, 2025
• Results First Posted: July 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)