BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BI-6727; Drug: BI 6727

• Registration Number: NCT00969761
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events when combined with a platinum therapy (cisplatin or carboplatin).

Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727 combination treatment with cisplatin and carboplatin.

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 Start: 2009-08
• Study First Submitted: 2009-08-31
• Study First Submitted QC: 2009-08-31
• Study First Posted: 2009-09-01
• Primary Completion: 2011-11
• Study Completion: 2012-02
• Results First Submitted: 2017-10-23
• Status Verified: 2018-08
• Results First Submitted QC: 2018-08-21
• Last Update Submitted: 2018-08-21
• Results First Posted: 2019-01-31
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B. BI 6727-carboplatin	BI-6727	patient to receive 3-weekly infusion escalating dose of BI 6727 combined to carboplatin
A. BI 6727-cisplatin	BI 6727	patient to receive 3-weekly infusion escalating dose of BI 6727 combined to cisplatin

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	3 weeks	The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin.; 0=not maximum tolerated dose, 1=was maximum tolerated dose.

Secondary Outcome Measures

Name	Time	Method
Duration of Objective Response	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria.; Tumour response was documented using appropriate techniques
Best Overall Response	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria.
Progression-free Survival	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first.
Incidence and Intensity of Adverse Events According to CTCAE Version 3.0	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0
Change From Baseline in Pulse Rate	Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Change from baseline in pulse rate at last value on treatment
Change From Baseline in Neutrophils	Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Change from baseline in neutrophils with the maximum value on treatment
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment.; Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Total Plasma Clearance After Intravascular Administration (CL)	1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion	Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.
Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils \>=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment.; Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)
Objective Response Rate	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0).; Tumour response was documented using appropriate techniques
Percentage of Participants With Significant Adverse Events	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE.; DLTs (i.e. significant AEs) per protocol were: * drug related CTCAE grade 3 or 4 non haematological toxicity (except vomiting or diarrhoea responding to supportive treatment and ototoxicity); * drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection; * drug related CTCAE Grade 4 thrombocytopenia; * drug related febrile neutropenia grade 3 (ANC\<1000/mm³ and fever≥ 38.5°C)
Percentage of Participants With Dose Limiting Toxicities	3 weeks	Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle.
Disease Control Rate	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria.
Duration of Disease Control	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first.
Percentage of Participants With Serious Adverse Events	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with serious adverse events (AEs)
Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)	1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion	Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.
Change From Baseline in Platelets	Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Change from baseline in platelets with the maximum value on treatment
Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets \>=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline.; The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment.; Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Worst CTCAE Grade on Treatment for Platelets	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Worst CTCAE Grade on Treatment for Neutrophils	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment	From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days	Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment.; Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)

Trial Locations

Locations (2)

1230.6.3201 Boehringer Ingelheim Investigational Site; 🇧🇪 Bruxelles, Belgium

1230.6.3202 Boehringer Ingelheim Investigational Site; 🇧🇪 Leuven, Belgium