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.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study Overview
Brief 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.
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
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
40 mg BI 836880
40 mg BI 836880
Intervention: BI 836880 (Drug)
120 mg BI 836880
120 mg BI 836880
Intervention: BI 836880 (Drug)
150 mg BI 836880
150 mg BI 836880
Intervention: BI 836880 (Drug)
180 mg BI 836880
180 mg BI 836880
Intervention: BI 836880 (Drug)
240 mg BI 836880
240 mg BI 836880
Intervention: BI 836880 (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Number of Participants With Drug-related Adverse Events (AEs) Leading to Dose Reduction or Discontinuation During the Treatment Period(From first trial drug administration until 42 (Residual Effect Period) days after the last trial drug administration, up to 566 days.)