This study is open to adults with advanced colorectal cancer or with advanced pancreatic cancer. The study has 2 parts. In the first part, participants with colorectal cancer get a medicine called BI 905711 combined with chemotherapy and bevacizumab. The purpose of the first part is to find the highest BI 905711 dose participants can tolerate. In the second part, participants with colorectal cancer or pancreatic cancer get BI 905711 combined with chemotherapy. Some participants also get bevacizumab. The second part tests whether BI 905711 makes tumours shrink. Participants get BI 905711, chemotherapy and bevacizumab about every 2 weeks as an infusion into a vein. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors regularly check the health of the participants and note any health problems that could have been caused by the study treatment. The doctors also monitor the size of the tumour.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
BI 905711
FOLFIRI
Bevacizumab
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
UZ Leuven
Leuven, Belgium
Beijing Cancer Hospital
Beijing, China
HOP la Milétrie
Poitiers, France
National Cancer Center Hospital East
Chiba, Kashiwa, Japan
Determination of the Maximum Tolerated Dose (MTD) of BI 905711
Maximum tolerated dose (MTD) was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. The MTD was to be considered reached if one of the following criteria was fulfilled: the posterior probability of the true DLT rate in the target interval (0.16, 0.33) of the MTD was above 0.5, or at least 12 patients had been treated in Phase Ia, of which at least 6 at the MTD.
Time frame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the residual effect period (REP) (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation
Number of patients with dose limiting toxicity (DLT) during MTD evaluation is presented.
Time frame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the REP (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
Confirmed Objective Response (OR)
Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for target lesions and assessed by MRI in patients with measurable disease, defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy.
Time frame: From the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, up to 54 weeks.
Number of PDAC Patients With DLTs During the MTD Evaluation Period Assessed in the First 6 Patients
In safety run-in part of Pancreatic Ductal Adenocarcinoma (PDAC) cohort. Number of PDAC patients with DLTs during the MTD evaluation period assessed in the first 6 patients is presented.
Time frame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the REP (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.
Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax)
Maximum measured plasma concentration of BI 905711 during the first cycle (Cmax) in phase Ia is presented.
Time frame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Maximum Measured Plasma Concentration of BI 905711 After Multiple Cycles (Cmax)
Maximum measured plasma concentration of BI 905711 after multiple cycles (Cmax) in phase Ia is presented.
Time frame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Area Under the Concentration-time Curve in Plasma of BI 905711 During the First Cycle (AUC0-336)
Area under the concentration-time curve in plasma of BI 905711 during the first cycle (AUC0-336) in phase Ia is presented.
Time frame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Area Under the Concentration Time-curve in Plasma of BI 905711 After Multiple Cycles (AUC0-336)
Area under the concentration time-curve in plasma of BI 905711 after multiple cycles (AUC0-336) in phase Ia is presented.
Time frame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Progression Free Survival (PFS)
Progression-Free Survival (PFS) defined from date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1 is presented.
Time frame: From date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1., up to 54 weeks.
Maximum Percentage Change From Baseline in the Sum of Longest Target Lesion Diameters
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Radiological (CT Scan) tumor shrinkage, defined as the difference between the minimum post-baseline sum of longest diameters of target lesions and the baseline sum of longest diameters of the same set of target lesions according to RECIST 1.1. is presented. Negative values indicate a reduction in the sum of target lesion diameters and positive values indicate an increase. Median change from baseline was calculated for each patient and then summarized over all patients.
Time frame: At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 54 weeks.
Duration of Objective Response (OR)
The duration of OR is measured from the time measurement criteria are first met for complete response (CR)/ partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded on study) according to RECIST 1.1. .
Time frame: From the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented, up to 54 weeks.
Disease Control
Disease control, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting at least 16 weeks according to RECIST 1.1 from the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy.
Time frame: From the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy, up to 54 weeks.
Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax) in Phase Ib
Maximum measured plasma concentration of BI 905711 during the first cycle (Cmax) in phase Ib is presented.
Time frame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Maximum Measured Plasma Concentration of BI 905711 After Multiple Cycles (Cmax) in Phase Ib
Maximum measured plasma concentration of BI 905711 after multiple cycles (Cmax) in phase Ib is presented.
Time frame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Area Under the Concentration-time Curve of BI 9057 During the First Treatment Cycle (AUC0-t2) in Phase Ib
Area under the concentration-time curve of BI 9057 during the first treatment cycle (AUC0-t2) in phase Ib is presented.
Time frame: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Area Under the Concentration-time Curve of BI 9057 After Multiple Cycles (AUC0-t2) in Phase Ib
Area under the concentration-time curve of BI 9057 after multiple cycles (AUC0-t2) in phase Ib is presented.
Time frame: Cycle 3: At 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.