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A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation)

Phase 1
Active, not recruiting
Conditions
Solid Tumors, KRAS Mutation; SOS1
Interventions
Registration Number
NCT04111458
Lead Sponsor
Boehringer Ingelheim
Brief Summary

This is a study in adults with advanced cancer (solid tumours) in whom previous chemotherapy was not successful. Only people who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster.

The study tests 2 medicines called BI 1701963 and trametinib. BI 1701963 prevents reactivation of KRAS. In this study, BI 1701963 is given to humans for the first time. Trametinib is an approved medicine (MEK inhibitor).

The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with trametinib the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with trametinib is able to make tumours shrink.

Participants can stay in the study as long as they benefit from treatment and can tolerate it.

During this time, they get tablets of BI 1701963 and trametinib once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
71
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
BI 1701963 + TrametinibBI 1701963-
BI 1701963 monotherapyBI 1701963-
BI 1701963 + TrametinibTrametinib-
Primary Outcome Measures
NameTimeMethod
Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)4 weeks
Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment periodUp to 3 years
Dose confirmation (Part B) and expansion (Part C) - Objective responseUp to 3 years
Secondary Outcome Measures
NameTimeMethod
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma)Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)Up to 5 weeks
Dose confirmation (Part B) and expansion (Part C) - Progression-free survival6 months
Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma)Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)Up to 5 weeks
Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR)Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres)Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment periodUp to 3 years
Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment periodUp to 3 years

Trial Locations

Locations (8)

Sarah Cannon Research Institute-Nashville-48456

🇺🇸

Nashville, Tennessee, United States

Erasmus Medisch Centrum-ROTTERDAM-50697

🇳🇱

Rotterdam, Netherlands

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Universitätsklinikum Frankfurt

🇩🇪

Frankfurt am Main, Germany

Universitätsklinikum Köln (AöR)

🇩🇪

Köln, Germany

Universitair Medisch Centrum Utrecht

🇳🇱

Utrecht, Netherlands

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