NeoplasmsPhase 1NCT02689505
Weekly BI 836880 in Patients With Advanced Solid Tumors
A Phase 1 study testing BI 836880 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in 2 countries.
Trial summary
This is a Phase I, multi-centre, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously once a week. The eligible patient population will be patients with advanced solid tumors. 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 4 Apr 2016to 31 Jul 2019
- 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
- 1 Age >=18 years 2. Histologically 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. patients do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD.
- 3. ECOG performance status <= 2 4. Adequate hepatic, renal and bone marrow functions as defined by the following criteria:
- Total bilirubin within normal limits (<= 1.5x upper limit of normal (ULN) for patient with Gilberts syndrome)
- Alanine amino transferase (ALT) and aspartate amino transferase (AST) <= 1.5x ULN (< 5x upper limit of normal (ULN) for patient known liver metastases)
- Serum creatinine < 1.5x ULN
- International normalized Ratio (INR) 0.8-1.2 or partial thromboplastin time (PTT) < 1.5x ULN
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- Absolute neutrophil count (ANC) > 1.5 109/L
- Platelet count > 100x109/ L.
- Haemoglobin > 10 g/dl (without transfusion within previous week) 5. Signed and dated written informed consent. 6. Life expectancy >= 3 months in the opinion of the investigator 7. Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade1, except for alopecia (any grade), sensory peripheral neuropathy CTCAE grade <= 2 or considered by the investigator as clinically not significant.
- 8. Male or female patients. Women of childbearing potential must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation [ICH M3(R2)] in combination with male condom as "double barrier", during the trial and for at least 6 months after the end of treatment with BI 836880, that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
- Male patient must always use condoms when sexually active during the trial and for at least 6 months after the end of treatment with BI 836880.
- Women of childbearing potential are defined as: Any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential" as described below.
- Women not of childbearing potential are defined as:
- Women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g., hysterectomy, bilateral oophorectomy or bilateral salpingectomy).
Who cannot join
- Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to the study drug according to the investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDS), inhaled corticosteroids, or the equivalent of < 10 mg/day prednisone)
- Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter at the start of study treatment.
- Serious concomitant disease (based on investigator judgement), especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
- Major injuries and/or surgery (as judged by the investigator) or bone fracture within 4 weeks of start of study 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 QT interval corrected for heart rate according to Fridericia's formula (QTcF) at baseline (> 470 ms). QTcF will be calculated by Investigator as the mean of the 3 ECGs taken at screening.
- Significant cardiovascular/ cerebrovascular disease (i.e uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > New York heart association ( NYHA II). Uncontrolled hypertension defined as: blood pressure in tested and relaxed condition >= 140 mmHg, systolic or > 90 mmHg diastolic (with or without medication), measured according to Section 5.3.2 and Appendix 10.2.
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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). No vitamin K antagonist and other anticoagulation allowed; low-molecular-weight heparin (LMWH) allowed only for prevention not for curative treatment.
- Use of alcohol or drug incompatible with patient participation in the study in the investigator opinion
- Patient unable or unwilling to comply with protocol
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
- Previous enrolment in this trial
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Weekly Repeated Intravenous Infusions in Patients With Advanced Solid Tumors.
This is a Phase I, multi-centre, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously once a week. The eligible patient population will be patients with advanced solid tumors.
The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for BI 836880 in patients with solid tumors. Preliminary safety data will be evaluated as secondary objectives.
Read more
Subsequently, pharmacokinetic profile, pharmacodynamic changes in circulating biomarkers and Dynamic Contrast-Enhanced Magnetic Resonance Imaging ( DCE-MRI), anti-tumor activity and the immunogenicity of BI 836880 will be explored up to a total of 40 patients with advanced solid tumors.
Dose escalation will be guided by a Bayesian logistic regression model with over dose control (EWOC) using at least 2 patients per dose cohorts.
Safety criteria will be followed, including adverse events according to Common Terminology Criteria (CTCAE version 4.03), incidence of dose limiting toxicities, physical examination, vital signs, safety laboratory parameters and Eastern Cooperative Oncology Group (ECOG).
- 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
Solution for intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| 40 mg BI 836880 | Experimental | 40 mg BI 836880 Receives: Drug: BI 836880 |
| 120 mg BI 836880 | Experimental | 120 mg BI 836880 Receives: Drug: BI 836880 |
| 150 mg BI 836880 | Experimental | 150 mg BI 836880 Receives: Drug: BI 836880 |
| 180 mg BI 836880 | Experimental | 180 mg BI 836880 Receives: Drug: BI 836880 |
| 240 mg BI 836880 | Experimental | 240 mg 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)
Determination of the maximum tolerated dose (MTD) in participants with advanced solid tumors. MTD was defined as the highest dose with less than 25% risk of true DLT rate being above 33% in the MTD evaluation period, and could be considered reached if the probability that the true DLT rate was in the target interval (16% to 33%) was sufficiently large during the MTD evaluation period. The MTD evaluation period was defined as 3 weeks after first administration of treatment.
Measured: First treatment cycle, 3 weeks from first administration of trial treatment (MTD evaluation period).
Number of Participants With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
The following drug-related adverse events qualified as DLTs: Common Terminology Criteria for Adverse Events (CTCAE) grade 4 neutropenia >7 days or complicated by infection; grade >3 febrile neutropenia; grade = 4 thrombocytopenia; grade > 3 thrombocytopenia with bleeding; grade > 3 proteinuria > 3 non haematological toxicity except: Vomiting or diarrhea responding to supporting treatment, fatigue lasting for less than 4 days, transient grade 3 infusion reaction, any laboratory abnormality, which was considered not clinically relevant by the investigator or resolved spontaneously or could be resolved with appropriate treatment. Hypertension: increase of diastolic blood pressure (BP) by 15 mmHg, which could not be controlled by hypertensive medication and requires a dose reduction of BI 836880 for further treatment course. All related AE leading to an interruption of BI 836880 for more than 14 days until recovery to baseline.
Measured: First treatment cycle, 3 weeks from first administration of trial treatment (MTD evaluation period).
Secondary outcomes (1)
Number of Participants With Drug-related Adverse Events (AEs) Leading to Dose Reduction or Discontinuation During the Treatment Period
Number of Participants with drug-related adverse Events (AEs) leading to dose reduction or discontinuation during the treatment period.
Measured: From first trial drug administration until 42 (Residual Effect Period) days after the last trial drug administration, up to 566 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study start4 Apr 2016
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT02689505
- Sponsor's protocol ID
- 1336.6
- Other IDs
- 2015-001132-38, 2015
- Status last verified
- Sep 2025
- First submitted
- 23 Feb 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
- Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Weekly Repeated Intravenous Infusions in Patients With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT02689505
- Acronym / sponsor ID
- 1336.6
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2016 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 24 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, multi-centre, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously once a week. The eligible patient population will be patients with advanced solid tumors.
The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for BI 836880 in patients with solid tumors. Preliminary safety data will be evaluated as secondary objectives.
Subsequently, pharmacokinetic profile, pharmacodynamic changes in circulating biomarkers and Dynamic Contrast-Enhanced Magnetic Resonance Imaging ( DCE-MRI), anti-tumor activity and the immunogenicity of BI 836880 will be explored up to a total of 40 patients with advanced solid tumors.
Dose escalation will be guided by a Bayesian logistic regression model with over dose control (EWOC) using at least 2 patients per dose cohorts.
Safety criteria will be followed, including adverse events according to Common Terminology Criteria (CTCAE version 4.03), incidence of dose limiting toxicities, physical examination, vital signs, safety laboratory parameters and Eastern Cooperative Oncology Group (ECOG).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 40 mg BI 836880 | Experimental | Drug: BI 83688040 mg BI 836880 |
| 120 mg BI 836880 | Experimental | Drug: BI 836880120 mg BI 836880 |
| 150 mg BI 836880 | Experimental | Drug: BI 836880150 mg BI 836880 |
| 180 mg BI 836880 | Experimental | Drug: BI 836880180 mg BI 836880 |
| 240 mg BI 836880 | Experimental | Drug: BI 836880240 mg BI 836880 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 1 Age >=18 years 2. Histologically 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. patients do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD.
- 3. ECOG performance status <= 2 4. Adequate hepatic, renal and bone marrow functions as defined by the following criteria:
- Total bilirubin within normal limits (<= 1.5x upper limit of normal (ULN) for patient with Gilberts syndrome)
- Alanine amino transferase (ALT) and aspartate amino transferase (AST) <= 1.5x ULN (< 5x upper limit of normal (ULN) for patient known liver metastases)
- Serum creatinine < 1.5x ULN
Key exclusion criteria (14 listed)
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 836880Solution for intravenous infusion | Drug | 120 mg BI 836880, 150 mg BI 836880, 180 mg BI 836880, 240 mg BI 836880, 40 mg BI 836880 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: First treatment cycle, 3 weeks from first administration of trial treatment (MTD evaluation period).
Determination of the maximum tolerated dose (MTD) in participants with advanced solid tumors. MTD was defined as the highest dose with less than 25% risk of true DLT rate being above 33% in the MTD evaluation period, and could be considered reached if the probability that the true DLT rate was in the target interval (16% to 33%) was sufficiently large during the MTD evaluation period. The MTD evaluation period was defined as 3 weeks after first administration of treatment.
Number of Participants With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
Time frame: First treatment cycle, 3 weeks from first administration of trial treatment (MTD evaluation period).
The following drug-related adverse events qualified as DLTs: Common Terminology Criteria for Adverse Events (CTCAE) grade 4 neutropenia >7 days or complicated by infection; grade >3 febrile neutropenia; grade = 4 thrombocytopenia; grade > 3 thrombocytopenia with bleeding; grade > 3 proteinuria > 3 non haematological toxicity except: Vomiting or diarrhea responding to supporting treatment, fatigue lasting for less than 4 days, transient grade 3 infusion reaction, any laboratory abnormality, which was considered not clinically relevant by the investigator or resolved spontaneously or could be resolved with appropriate treatment. Hypertension: increase of diastolic blood pressure (BP) by 15 mmHg, which could not be controlled by hypertensive medication and requires a dose reduction of BI 836880 for further treatment course. All related AE leading to an interruption of BI 836880 for more than 14 days until recovery to baseline.
1 secondary outcome
Number of Participants With Drug-related Adverse Events (AEs) Leading to Dose Reduction or Discontinuation During the Treatment Period
Time frame: From first trial drug administration until 42 (Residual Effect Period) days after the last trial drug administration, up to 566 days.
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.
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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
2 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 2 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 14 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 2 sites in France, Spain. 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: First treatment cycle, 3 weeks from first administration of trial treatment (MTD evaluation period).). 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 NCT02689505, 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.