Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BI 6727; Drug: BIBF 1120

• Registration Number: NCT01022853
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2009-11-26
• Study First Submitted QC: 2009-11-26
• Study Start: 2009-12
• Study First Posted: 2009-12-01
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2017-10
• Results First Submitted: 2017-10-23
• Results First Submitted QC: 2017-10-23
• Last Update Submitted: 2017-10-23
• Results First Posted: 2018-07-30
• Last Update Posted: 2018-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIBF 1120 and BI 6727	BI 6727	Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120
BIBF 1120 and BI 6727	BIBF 1120	Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD).	28 days	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
Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib	28 days	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Drug Related Adverse Events	From first study drug administration until 28 days after the last administration of any study medication, up to 485 days	Number of participants with investigator-defined drug related adverse events.
Number of Participants With Dose Limiting Toxicities	From first study drug administration until 28 days after the last administration of any study medication, up to 485 days	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
Cmax of Volasertib	0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion	Maximum measured concentration (Cmax) in plasma of Volasertib in Cycle 1.
CL of Volasertib	0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion	Total plasma Clearance (CL) of Volasertib in Cycle 1.
Vss of Volasertib	0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion	Volume of distribution at steady state (Vss) of Volasertib in Cycle 1.
Cmax of Nintedanib	5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9	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.
AUC(0-6h) of Nintedanib	5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9	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.
Tmax of Nintedanib	5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9	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.
Number of Patients With Best Overall Response	Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.	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.
Number of Patients With Objective Response (OR)	Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end 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.
Number of Patients With Disease Control	Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.	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.
Duration of Disease Control	Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.	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.
Progression Free Survival (PFS)	Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.	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).

Trial Locations

Locations (2)

1230.7.39002 Boehringer Ingelheim Investigational Site; 🇮🇹 Ancona, Italy

1230.7.39001 Boehringer Ingelheim Investigational Site; 🇮🇹 Milano, Italy