NeoplasmsPhase 1NCT02674152
Dose Finding Study of BI 836880 in Patients With Solid Tumors
A Phase 1 study testing BI 836880 in people with Neoplasms, run by Boehringer Ingelheim at 3 sites in 2 countries.
Trial summary
This is a Phase I, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously. The eligible patient population will be patients with advanced solid tumours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- BI 836880
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 5 Jan 2016to 4 Nov 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- Histologically or cytologically confirmed malignancy which is locally advanced or metastatic solid tumor, and either refractory after standard therapy for the disease or for which standard therapy is not reliably effective, e.g. they do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD.
- ECOG performance status <= 2
- Adequate hepatic, renal and bone marrow functions
- Signed written informed consent.
- Life expectancy min. 3 months in the opinion of the investigator
- Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade) sensory peripheral neuropathy CTCAE grade <= 2 or considered not clinically significant.
- adequate contraception by male and female patient during the trial and for at least 6 months after end of treatment.
Who cannot join
- Known hypersensitivity to the trial drugs or their excipients
- Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter of trial onset.
- Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug
- Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
- patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 470 ms). QTcF will be calculated by Investigator as the mean of the 3 ECGs taken at screening.
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II). Uncontrolled hypertension defined as: blood pressure in rested and relaxed condition >=140 mmHg systolic, or >=90 mmHg diastolic (with or without medication), measured according to protocol.
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- History of severe haemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
- Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
- Patient with brain metastases that are symptomatic and/or require therapy.
- Patients who require full-dose anticoagulation (according to local guidelines).
- Active alcohol or drug abuse in the opinion of the investigator.
- Patients who are under judicial protection and patients who are legally institutionalized.
- Patients unable or unwilling to comply with protocol
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Germany2 sites
Universitätsklinikum Augsburg
Augsburg, 86156
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
About this study
Official title: A First-in Human Phase I, Non-randomised, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Repeated Intravenous Infusions in Patients With Solid Tumors.
This is a Phase I, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously. The eligible patient population will be patients with advanced solid tumours. At any time during the trial, it will not be permitted to escalate to a dose which does not fulfil the escalation with overdose control (EWOC) criterion
- Conditions
- Neoplasms
- Being tested
- BI 836880
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 836880Drug
BI 836880
| Study group | Role | What they receive |
|---|---|---|
| 40 mg BI 836880 | Experimental | BI 836880 Receives: Drug: BI 836880 |
| 120 mg BI 836880 | Experimental | BI 836880 Receives: Drug: BI 836880 |
| 360 mg BI 836880 | Experimental | BI 836880 Receives: Drug: BI 836880 |
| 720 mg BI 836880 | Experimental | BI 836880 Receives: Drug: BI 836880 |
| 1000 mg BI 836880 | Experimental | BI 836880 Receives: Drug: BI 836880 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 0.33 during the MTD evaluation period, defined as 3 weeks after first administration of trial medication (i.e. cycle 1). Patients who did not complete the MTD evaluation period for reasons other than DLT were excluded from the analysis of the primary endpoint.
Measured: Up to 3 weeks after the first administration of trial medication.
Number of Patients With Dose-limiting Toxicities (DLT) in the Maximum Tolerated Dose (MTD) Period
DTLs are defined as followed:
- Drug-related Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non-haematological toxicity
- CTCAE Grade 4 neutropenia lasting >7 days or complicated by infection (please note that in case of grade 4 neutropenia a more frequent follow up of patient was necessary
- Febrile neutropenia of CTCAE Grade ≥3
- CTCAE Grade 4 thrombocytopenia or CTCAE Grade ≥3 thrombocytopenia with bleeding
- Treatment delay for >2 weeks due to unresolved drug-related AEs, which started within 3 weeks after the first treatment
- Hypertension: increase of diastolic blood pressure (DBP) by 15 millimetre of mercury (mmHg) confirmed by a second measurement or by ambulatory blood pressure measurement (when indicated, e.g. white coat effect) which could not be controlled by hypertensive medication and required a dose reduction of BI 836880 for further treatment cycle
- Proteinuria: urinary protein ≥3.5 gram/day (CTCAE Grade 3)
Measured: Up to 3 weeks after the first administration of trial medication.
Secondary outcomes (3)
Number of Patients With Drug-related Adverse Events Leading to Dose Reduction or Discontinuation During Treatment Period
Number of patients with drug-related adverse events leading to dose reduction or discontinuation during treatment period.
Measured: From first drug infusion until 42 days (residual effect period) after last drug infusion, up to 828 days.
Area Under the Serum Concentration-time Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-tz) After the First Dose
Area under the serum concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-tz) after the first dose.
Measured: 5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.
Terminal Half-life (t_1/2) of BI 836880
Terminal half-life (t_1/2) of BI 836880.
Measured: 5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2016 (estimated)
- Study start5 Jan 2016
- Primary completion12 Sep 2018
- Study completion4 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02674152
- Sponsor's protocol ID
- 1336.1
- Other IDs
- 2014-005395-28, 2014
- Status last verified
- Sep 2025
- First submitted
- 4 Jan 2016
- Last updated
- 1 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Keller S, Kunz U, Schmid U, Beusmans J, Buchert M, He M, Jayadeva G, Le Tourneau C, Luedtke D, Niessen HG, Oum'hamed Z, Pleiner S, Wang X, Graeser R. Comprehensive biomarker and modeling approach to support dose finding for BI 836880, a VEGF/Ang-2 inhibitor. J Transl Med. 2024 Oct 14;22(1):934. doi: 10.1186/s12967-024-05612-x.
PubMed 39402675Le Tourneau C, Becker H, Claus R, Elez E, Ricci F, Fritsch R, Silber Y, Hennequin A, Tabernero J, Jayadeva G, Luedtke D, He M, Isambert N. Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors. ESMO Open. 2022 Oct;7(5):100576. doi: 10.1016/j.esmoop.2022.100576. Epub 2022 Sep 13.
PubMed 36108560
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in Human Phase I, Non-randomised, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Repeated Intravenous Infusions in Patients With Solid Tumors.
- ClinicalTrials.gov ID
- NCT02674152
- Acronym / sponsor ID
- 1336.1
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 5 Jan 2016 (actual)
- Primary completion
- 12 Sep 2018 (actual)
- Study completion
- 4 Nov 2020 (actual)
- First posted
- 4 Feb 2016 (estimated)
- Results
- Posted 1 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously. The eligible patient population will be patients with advanced solid tumours. At any time during the trial, it will not be permitted to escalate to a dose which does not fulfil the escalation with overdose control (EWOC) criterion
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 40 mg BI 836880 | Experimental | Drug: BI 836880BI 836880 |
| 120 mg BI 836880 | Experimental | Drug: BI 836880BI 836880 |
| 360 mg BI 836880 | Experimental | Drug: BI 836880BI 836880 |
| 720 mg BI 836880 | Experimental | Drug: BI 836880BI 836880 |
| 1000 mg BI 836880 | Experimental | Drug: BI 836880BI 836880 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age >= 18 years
- Histologically or cytologically confirmed malignancy which is locally advanced or metastatic solid tumor, and either refractory after standard therapy for the disease or for which standard therapy is not reliably effective, e.g. they do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD.
- ECOG performance status <= 2
- Adequate hepatic, renal and bone marrow functions
- Signed written informed consent.
Key exclusion criteria (14 listed)
- Known hypersensitivity to the trial drugs or their excipients
- Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter of trial onset.
- Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug
- Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
- patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 470 ms). QTcF will be calculated by Investigator as the mean of the 3 ECGs taken at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 836880BI 836880 | Drug | 1000 mg BI 836880, 120 mg BI 836880, 360 mg BI 836880, 40 mg BI 836880, 720 mg BI 836880 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Up to 3 weeks after the first administration of trial medication.
Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 0.33 during the MTD evaluation period, defined as 3 weeks after first administration of trial medication (i.e. cycle 1). Patients who did not complete the MTD evaluation period for reasons other than DLT were excluded from the analysis of the primary endpoint.
Number of Patients With Dose-limiting Toxicities (DLT) in the Maximum Tolerated Dose (MTD) Period
Time frame: Up to 3 weeks after the first administration of trial medication.
DTLs are defined as followed: * Drug-related Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non-haematological toxicity * CTCAE Grade 4 neutropenia lasting >7 days or complicated by infection (please note that in case of grade 4 neutropenia a more frequent follow up of patient was necessary * Febrile neutropenia of CTCAE Grade ≥3 * CTCAE Grade 4 thrombocytopenia or CTCAE Grade ≥3 thrombocytopenia with bleeding * Treatment delay for >2 weeks due to unresolved drug-related AEs, which started within 3 weeks after the first treatment * Hypertension: increase of diastolic blood pressure (DBP) by 15 millimetre of mercury (mmHg) confirmed by a second measurement or by ambulatory blood pressure measurement (when indicated, e.g. white coat effect) which could not be controlled by hypertensive medication and required a dose reduction of BI 836880 for further treatment cycle * Proteinuria: urinary protein ≥3.5 gram/day (CTCAE Grade 3)
3 secondary outcomes
Number of Patients With Drug-related Adverse Events Leading to Dose Reduction or Discontinuation During Treatment Period
Time frame: From first drug infusion until 42 days (residual effect period) after last drug infusion, up to 828 days.
Area Under the Serum Concentration-time Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-tz) After the First Dose
Time frame: 5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.
Terminal Half-life (t_1/2) of BI 836880
Time frame: 5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39402675Keller S, Kunz U, Schmid U, Beusmans J, Buchert M, He M, Jayadeva G, Le Tourneau C, Luedtke D, Niessen HG, Oum'hamed Z, Pleiner S, Wang X, Graeser R. Comprehensive biomarker and modeling approach to support dose finding for BI 836880, a VEGF/Ang-2 inhibitor. J Transl Med. 2024 Oct 14;22(1):934. doi: 10.1186/s12967-024-05612-x.
- Derived from this study: PubMed 36108560Le Tourneau C, Becker H, Claus R, Elez E, Ricci F, Fritsch R, Silber Y, Hennequin A, Tabernero J, Jayadeva G, Luedtke D, He M, Isambert N. Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors. ESMO Open. 2022 Oct;7(5):100576. doi: 10.1016/j.esmoop.2022.100576. Epub 2022 Sep 13.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 836880 in people with Neoplasms, run by Boehringer Ingelheim at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Up to 3 weeks after the first administration of trial medication.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02674152, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.