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Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120

BI 6727

BIBF 1120

Boehringer Ingelheim

The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of BI 6727 in combination with fixed dose BIBF 1120, in patients with advanced or metastatic solid tumours.

Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors

An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBF 1120 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit

DLT was defined as:

1. Drug-related CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or
2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
3. CTCAE grade 4 thrombocytopenia

The MTD was determined using a 3+3 design with de-escalation. The MTD was defined as the highest dose level at which maximal 1 out of 6 patients experienced DLT in the first course of the escalation nd de-escalation phase. However, all DLT's occurring in the trial were considered for selection of the recommended dose for further development.

Number of participants with investigator-defined drug related adverse events.

Number of participants with dose limiting toxicities (DLTs).

DLT was defined as:

1. Drug-related CTCAE grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or
2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
3. CTCAE grade 4 thrombocytopenia

Maximum measured concentration (Cmax) in plasma of Volasertib in Cycle 1.

Total plasma Clearance (CL) of Volasertib in Cycle 1.

Volume of distribution at steady state (Vss) of Volasertib in Cycle 1.

Maximum measured concentration (Cmax) of Nintedanib in Cycle 1.

400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.

Area under the concentration-time curve (AUC) of Nintedanib over the time interval 0 to 6 hours in Cycle 1.

400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.

Time from dosing to the maximum measured concentration, Cmax, of Nintedanib (tmax) in Cycle 1.

400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.

Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as the best overall response (complete response, partial response, stable disease, progressive disease or not evaluable) since the start of treatment.

Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR) as best response throughout the study.

Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Disease control is defined as complete response (CR), partial response (PR) or stable disease (SD) as best response throughout the study.

Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.

PFS is defined as the time from start of treatment with study medication to tumour progression or death whichever occurs first. Tumour response was to be documented using appropriate techniques such as magnetic resonance imaging (MRI) or computer tomography (CT).

Patients were asked for spontaneous reports about AEs; detailed information was collected by specific questions.

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 100 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day.

Course 2 and subsequent courses comprised 21 days. Volasertib was infused on Day 1 and continuous nintedanib administration re-started on Day 2.

100 mg Volasertib + 200 mg Nintedanib

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 200 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day.

Course 2 and subsequent courses comprised 21 days. Volasertib was infused on Day 1 and continuous nintedanib administration re-started on Day 2.

200 mg Volasertib + 200 mg Nintedanib

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 300 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day.

Course 2 and subsequent courses comprised 21 days. Volasertib was infused on Day 1 and continuous nintedanib administration re-started on Day 2.

300 mg Volasertib + 200 mg Nintedanib

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 350 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day.

Course 2 and subsequent courses comprised 21 days. Volasertib was infused on Day 1 and continuous nintedanib administration re-started on Day 2.

350 mg Volasertib + 200 mg Nintedanib

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 400 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day.

400 mg Volasertib + 200 mg Nintedanib

Total

Age, Continuous

Sex: Female, Male

Treated Set - All patients who received ≥1 dose of study medication were included in the treated set.

Boehringer Ingelheim Call Center

Treated set. All patients who received ≥1 dose of study medication were included in the treated set.

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD).

Number of Participants With Drug Related Adverse Events

Number of Participants With Dose Limiting Toxicities

Pharmacokinetic (PK) analysis set. The PK analysis set included all patients who took at least 1 dose of study medication and provided at least 1 blood sample following drug administration.

Cmax of Volasertib

CL of Volasertib

Vss of Volasertib

Cmax of Nintedanib

AUC(0-6h) of Nintedanib

Tmax of Nintedanib

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Missing

Number of Patients With Best Overall Response

Objective Response (OR)

Course 1 comprised of 28 days because of a 7-day run-in period for nintedanib (200 mg twice daily). The treatment with nintedanib started on Day 1 of Course 1 and continued until the end of the course. 100 mg volasertib was infused on Day 8 of Course 1; no nintedanib was to be taken on that day. Course 2 and subsequent courses comprised 21 days. Volasertib was infused on Day 1 and continuous nintedanib administration re-started on Day 2.

Number of Patients With Objective Response (OR)

All patients received both Volasertib and Nintedanib. Starting dose of Volasertib was 100 mg, the next dose levels were 200 mg, 300 mg, 350 mg and 400 mg, which was to be infused on Day 8 in Course 1 and on Day 1 of subsequent courses. 200 mg Nintedanib was continuously administered twice daily except for the day of Volasertib administration.

Volasertib in Combination With Nintedanib

Treated Set. All patients who received \>= 1 dose of study medication.

Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib

Number of Patients With Disease Control

All patients received both Volasertib and Nintedanib. Volasertib was to be infused on Day 8 in Course 1 and on Day 1 of subsequent courses, dose level varied between 100mg and 400mg. 200 mg Nintedanib was continuously administered twice daily except for the day of Volasertib administration.

Spots Global Cancer Trial Database for Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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