Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours

An Open-label Phase I Dose Escalation Trial of Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours

This open-label dose escalation phase I trial, 1280.15, is with the first administration of BI 836845 in Japanese patients with various types of advanced solid tumours. The rationale behind this study is to identify the maximum tolerated dose (MTD) of BI 836845 in Japanese patients with advanced solid tumours as weekly intravenous administration.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: 750 milligram Xentuzumab; Drug: 1000 milligram Xentuzumab; Drug: 1400 milligram Xentuzumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Patients who meet all of the following inclusion criteria by the judgment of investigator are eligible to receive the study treatment:

1. Patients with cytologically or histologically confirmed solid tumours that are refractory to standard therapy, for whom no standard therapy of proven efficacy exists, or who are not amenable to establish treatment options
2. Age >=20 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
4. Written informed consent that is consistent with Good Clinical Practice (GCP) guidelines

Exclusion criteria:

Patients who apply any of the following exclusion criteria by the judgment of investigator are not eligible to receive the study treatment:

1. Active infectious disease to be incompatible with the study treatment

2. Patients who do not have sufficient major organ function and meet any of the following test results at screening period

   • Cardiac left ventricular function with resting ejection fraction <=50% as determined by echocardiography (ECHO) or multiple-gated acquisition scan (MUGA)
   • Absolute neutrophil count <1500/µL
   • Platelets <100 000/µL
   • Total bilirubin >1.5 × the upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 × ULN (in case of known liver metastases, AST and/or ALT >5 × ULN)
   • Creatinine >1.5 × ULN
   • Haemoglobin <9 g/dL
   • HbA1c >=8% and fasting glucose >8.9 mmol/L (>160 mg/dL)
3. Serious illness or concomitant non-oncological disease including severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may compromise the safety of the patient during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results considered by the investigator to be incompatible with the study treatment
4. History of thrombosis (except tumour invading great vessels) within 1 year before start of study treatment or if concurrent anticoagulation required
5. Patients not recovered from any therapy-related toxicities from previous chemotherapies, hormonal therapies, immunotherapies, molecular-targeted therapies, or radiotherapies to Common Terminology Criteria for Adverse Events (CTCAE) grade <=1
6. Patients who have not recovered from any previous surgery and major surgery within the last 4 weeks before start of study treatment
7. Patients with untreated or symptomatic brain metastases.
8. Patients who have been treated with any of the following within 4 weeks before start of study treatment: chemotherapies, immunotherapies, radiotherapies (within 2 weeks before start of study treatment for local palliative radiotherapies for the treatment of brain metastasis or extremities), biological therapies, molecular-targeted therapies, hormonal therapies for breast cancer within 2 weeks before start of study treatment, or treatment with other investigational drugs.
9. Patients who have used any investigational drug within 4 weeks before start of study treatment or who have planned concomitantly use with the trial.
10. Patients unable to comply with the clinical trial protocol (CTP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 750 milligram Xentuzumab; 750 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.	Drug: 750 milligram Xentuzumab; 750 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.; Other Names: BI 836845
Experimental: 1000 milligram Xentuzumab; 1000 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.	Drug: 1000 milligram Xentuzumab; 1000 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.; Other Names: BI 836845
Experimental: 1400 milligram Xentuzumab; 1400 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.	Drug: 1400 milligram Xentuzumab; 1400 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.; Other Names: BI 836845

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Xentuzumab in Japanese Patients With Advanced Solid Tumours, as Identified by the Number of Patients With Dose-limiting Toxicities (DLTs)	MTD of xentuzumab in Japanese patients with advanced solid tumours, as identified by the number of patients with DLTs. The MTD of xentuzumab was defined as the highest dose tested with DLT occurring in not more than 1 out of 6 evaluable patients. DLTs were defined as: Haematological toxicities: Common Terminology Criteria for Adverse Events (CTCAE) grade (g) 4 neutropenia ≥7 days (d), select cases of Febrile neutropenia, Infections or CTCAE g4 thrombocytopenia or CTCAE g3 thrombocytopenia. Non-haematological toxicities: CTCAE grade 3 or 4 non-haematologic toxicity, with exceptions CTCAE grade≥2 infusion reaction or nausea and/or vomiting with exceptions CTCAE grade ≥3 skin toxicity, hyperglycaemia, any electrolyte adverse events (AE), fatigue or asthenia with exceptions No recovery from a non-DLT CTCAE g≥3 toxicity to g≤1 within 14 d of administered dose Other drug-related AEs (CTCAE g2), might qualify as a DLT, which will be determined on a case by case bases.	During the first cycle of treatment, up to 21 days of treatment.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• Doi T, Kuboki Y, Naito Y, Ishida M, Tanaka T, Takeuchi Y. A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors. Cancer Sci. 2022 Mar;113(3):1010-1017. doi: 10.1111/cas.15231. Epub 2022 Jan 13.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 14, 2023

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimated): May 23, 2014

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 1280.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing