Dose Finding Study of BI 836880 in Patients With Solid Tumors

NCT02674152 | Completed Phase 1 Results

• 2 other identifiers: 1336.12014-005395-28
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 3

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  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

  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

  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

  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.

Study Arms (5)

40 mg BI 836880

EXPERIMENTAL

BI 836880

Drug: BI 836880

120 mg BI 836880

EXPERIMENTAL

BI 836880

Drug: BI 836880

360 mg BI 836880

EXPERIMENTAL

BI 836880

Drug: BI 836880

720 mg BI 836880

EXPERIMENTAL

BI 836880

Drug: BI 836880

1000 mg BI 836880

EXPERIMENTAL

BI 836880

Drug: BI 836880

Interventions

BI 836880 DRUG

BI 836880

1000 mg BI 836880; 120 mg BI 836880; 360 mg BI 836880; 40 mg BI 836880; 720 mg BI 836880

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

INS Curie

Paris, 75248, France

Location

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Related Publications (2)

• 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.

  PMID: 39402675 DERIVED

• Le 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.

  PMID: 36108560 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

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: January 4, 2016
• First Posted: February 4, 2016
• Study Start: January 5, 2016
• Primary Completion: September 12, 2018
• Study Completion: November 4, 2020
• Last Updated: October 1, 2025
• Results First Posted: October 1, 2025

Record last verified: 2025-09

Locations

FR (1); DE (2)