This study is open to adults with advanced bowel cancer (colorectal cancer) with a KRAS mutation. This is a study in people for whom previous treatment was not successful and surgery is not a treatment option. The purpose of this study is to find the highest dose of BI 1701963 that people with bowel cancer can tolerate when taken together with a medicine called irinotecan. The study also tests whether BI 1701963 in combination with irinotecan is able to make tumours shrink. BI 1701963 may help to turn off KRAS. Activating KRAS mutations make tumours grow. Irinotecan is a medicine to treat bowel cancer. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, participants take BI 1701963 as tablet once a day and get irinotecan as infusion every two weeks. The doctors regularly monitor the size of the tumour. The doctors also collect information on any health problems of the participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Tablet
Solution for infusion
Shanghai East Hospital, Tongji University China
Shanghai, China
Maximum tolerated dose (MTD) based on the number of dose limiting toxicities (DLTs) in the MTD evaluation period
Combination dose escalation part (Part B)
Time frame: 28 days
Number of patients experiencing DLTs in the MTD evaluation period
Combination dose escalation part (Part B)
Time frame: 28 days
Objective Response (OR) according to RECIST version 1.1
Combination therapy expansion part (Part C)
Time frame: 28 days per treatment cycle.
Number of patients with DLTs in the first treatment cycle
Monotherapy safety run-in part (Part A)
Time frame: 28 days
Maximum measured concentration of BI 1701963 in plasma (Cmax)
Monotherapy safety run-in part (Part A)
Time frame: 28 days per treatment cycle.
Area under the concentration time curve of BI 1701963 in plasma over the time interval from 0 to the last quantifiable plasma concentration (AUC0-tz)
Monotherapy safety run-in part (Part A)
Time frame: 28 days per treatment cycle.
Area under the concentration-time curve of BI 1701963 in plasma over the dosing interval τ at steady state (AUCτ(,ss))
Monotherapy safety run-in and combination dose escalation part (Part A+B)
Time frame: 28 days per treatment cycle.
Maximum measured concentration of BI 1701963 in plasma at steady state over a uniform dosing interval tau (Cmax,ss)
Monotherapy safety run-in and combination dose escalation part (Part A+B)
Time frame: 28 days per treatment cycle.
Duration of objective response (DOR)
Combination therapy expansion part (Part C)
Time frame: 28 days per treatment cycle.
Tumour shrinkage (in millimetres)
Combination therapy expansion part (Part C)
Time frame: 28 days per treatment cycle.
Progression-free survival (PFS)
Combination therapy expansion part (Part C)
Time frame: Up to 6 months.
Number of patients experiencing grade ≥3 treatment-related AEs during the entire treatment period
Combination therapy expansion part (Part C)
Time frame: 28 days per treatment cycle.
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