Clinical trial NCT04147247: A Trial to Find the Safe Dose for BI 905681 in Patients With Incurable Tumours or Tumours That Have Spread
Official title: An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 905681 Administered Intravenously in Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-11-01
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) of BI 905681 given as an intravenous infusion and to determine the recommended dose and dosing schedule for further trials in the development of BI 905681. The MTD will be defined based on the frequency of patients experiencing dose-limiting toxicities (DLTs) during the MTD/DLT evaluation period, which is defined as the first cycle of treatment. Separate MTDs will be determined for Schedule A and Schedule B.

The secondary objective of the trial is to determine the pharmacokinetic (PK) profile of BI 905681.

Detailed description: Study was opened to recruitment until 29-Oct-2021, however from 15-Apr-2021 no patient was recruited.

Eligibility criteria: Inclusion criteria:

* Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1).
* Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.
* Patients willing to undergo mandatory tumour biopsy at the time points specified in the protocol.
* Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 (R01-0787).
* Adequate organ function defined as all of the following:

  * Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L; haemoglobin ≥9.0 g/dL; platelets ≥100 x 10\^9/L without the use of haematopoietic growth factors within 4 weeks of start of study medication.
  * Total bilirubin ≤1.5 x the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN.
  * Creatinine ≤1.5 x ULN. If creatinine is \>1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥50 ml/min (measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
  * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤5 x ULN
  * Alkaline Phosphatase (ALP) \<5 x ULN
* At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
* Signed and dated written informed consent in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial
* Life expectancy ≥3 months at the start of treatment in the opinion of the investigator
* Further inclusion criteria apply

Exclusion criteria:

* Osteoporosis ≥ CTCAE Grade 2
* Osteoporotic compression fracture within 12 months prior to informed consent which is clinically significant in the opinion of the investigator.
* Further exclusion criteria apply

Primary outcomes:
measure: The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681
timeFrame: The first cycle of treatment, up to 21 days.
measure: Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period
timeFrame: From the first administration of study till the last administration of study drug +42 days, up to 126 days.
Secondary outcomes:
measure: Cmax: Maximum Measured Concentration of BI 905681 in Serum After First Infusion
timeFrame: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.
measure: AUC0-tz: Area Under the Serum Concentration-time Curve Over the Time Interval From 0 to the Last Measured Time Point (tz)
timeFrame: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
Study officials:
References: