BI 6727 Administered Intravenously Every 3 Weeks in Patients With Solid Tumours

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BI 6727

• Registration Number: NCT02273388
• 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. Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-11-04
• Primary Completion: 2009-01-19
• Study First Submitted: 2014-10-23
• Study First Submitted QC: 2014-10-23
• Study First Posted: 2014-10-24
• Study Completion: 2021-04-06
• Results First Submitted: 2022-04-06
• Status Verified: 2022-12
• Results First Submitted QC: 2022-12-01
• Last Update Submitted: 2022-12-01
• Results First Posted: 2023-10-03
• Last Update Posted: 2023-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
400 mg BI 6727	BI 6727	-
450 mg BI 6727	BI 6727	-
12 mg BI 6727	BI 6727	-
24 mg BI 6727	BI 6727	-
48 mg BI 6727	BI 6727	-
75 mg BI 6727	BI 6727	-
125 mg BI 6727	BI 6727	-
200 mg BI 6727	BI 6727	-
300 mg BI 6727	BI 6727	-
300 mg BI 6727 1h2h	BI 6727	Infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2.
300 mg BI 6727 2h1h	BI 6727	Infusion over 2 hours (2h) in course 1 and over 1 hours (1h) in course 2.
350 mg BI 6727	BI 6727	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	21 days (first treatment course).	MTD is defined as: the dose of BI 6727 which is one dose tier below that dose at which two or more out of a maximum of six patients experienced dose-limiting toxicity (DLT). At the maximum tolerated dose, no more than one patient out of six patients may experience DLT, i.e. MTD is defined as the highest dose studied for which the incidence of dose-limiting toxicity is no more than 17% (i.e. 1/6 patients) during the first course.; DLT is defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or 4 non haematological toxicity (except emesis or diarrhoea responding to supportive treatment), or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection, or CTCAE Grade 4 thrombocytopenia .

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Progression	Up to 814 days.	Number of participants with progression of disease.; Progressive disease is defined according to the Response Evaluation Criteria in Solid Tumours (RECIST) as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter.
Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz).
Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24)	5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.	Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 24 hours (Ae0-24).
Number of Participants With Adverse Events (AEs)	From first drug administration until last drug administration plus 21 days, up to 835 days.	Number of participants with adverse events. The events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3.0.; Grade refers to the severity of adverse event. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.
Number of Participants With Clinically Relevant Abnormalities	From baseline to the last value on treatment, up to 814 days.	Number of participants with clinically relevant abnormalities, occurring in \>5% of the total number of participants, is reported.; Clinically relevant post baseline values with Common Terminology Criteria for Adverse Events (CTCAE) grades: * CTCAE grade ≥4 for White blood cell count (WBC) , Neutrophils (NEUT), NEUABS Lymphocytes (LMPH) if baseline CTCAE grade is not 4; * CTCAE grade ≥3 for Haemoglobin (HGB), Platelets count (PLTCT), Alkaline phosphatase (ALKP), serum glutamic-oxaloacetic-transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total bilirubin (TBILI), if baseline CTCAE grade is ≥3 increases of one grade; * CTCAE grade ≥2 for other parameters, if baseline CTCAE grade is ≥2 increases of at least one grade
Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score	At baseline and at end of treatment (up to 814 days).	ECOG score: The scale of ECOG score is defined as a six point categorical scale as described ranging from 0 (asymptomatic) to 5 (death). ECOG score change from baseline to end of treatment is calculated, and defined as; = ECOG score at end of treatment - ECOG score at baseline.; Scale of ECOG score change: The ECOG score changes from baseline score are categorized on a three point categorical scale: Improved, unchanged, and deteriorated. Improvement or deterioration of performance status required a decrease or an increase from baseline, respectively, of at least one point on the ECOG scale. The number of patients per category ("improved", "unchanged", "deteriorated" "unknown") is reported.
Electrocardiogram (ECG) - QTcF Change From Baseline	At baseline and 5 minutes before infusion end, 1 hour after end of infusion and at 4 and 12 hours after start of infusion, at course 1.	Electrocardiogram (ECG) - QTcF change from baseline. QTcF intervals form the ECGs were analysed for changes during and after intravenous infusion of BI 300 mg dose over 1 hours and over 2 hours. For baseline ECG, the combined baseline, defined as the mean of the 2 triplicates at the time-point closest to but prior to the start of the infusion of both treatment courses, i.e. a common baseline is used for both treatment courses, was used. Mean is adjusted mean.; Abbreviations: QTcF: QT interval, corrected for heart rate according to Fridericia's formula (seconds) = measured QT / (cube root of preceding RR interval) QT: Interval from the beginning of the Q wave to the end of the T wave on an ECG (seconds).; CfB: Change from baseline.
Vital Signs - Blood Pressure	At baseline.	Systolic blood pressure and diastolic blood pressure are reported.
Vital Signs - Pulse Rate	At baseline.	Pulse rate is reported.
Time From Dosing to Maximum Concentration (Tmax)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Time from dosing to maximum concentration (tmax).; Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).; For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)	0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion. (*Immediately prior to end of infusion of BI 6727).	Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz)	0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 to the last quantifiable time point tz (AUC0-tz).; Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).; For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Terminal Rate Constant in Plasma (λz)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Terminal rate constant in plasma (λz).
Terminal Half-life of the Analyte in Plasma (t1/2)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Terminal half-life of the analyte in plasma (t1/2).
Number of Participants With Unconfirmed Best Overall Response	Up to 814 days.	For solid tumours, evaluation of tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST) definition. The overall response of target and non-target lesions together with or without the appearance of new lesions as reported by the investigator was assessed on a four point categorical scale as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the RECIST criteria. In order to best handle measurements that were non-evaluable (NEV) a modified version of the RECIST criteria was used. If a RECIST overall response was deemed NEV, it could be further classified into non-evaluable clinically progressive disease (NEVCPD ) or non-evaluable clinically non-progressive disease (NEVCNPD), depending on the subjective assessment of the investigator.
Maximum Concentration of BI 6727 in Plasma (Cmax)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Maximum concentration of BI 6727 in plasma (Cmax).; Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).; For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Apparent volume of distribution at steady state following intravascular administration (Vss).
Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Mean residence time of BI 6727 in the body after intravenous administration (MRT).
Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL)	At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).	Total clearance of BI 6727 in the plasma after intravascular adminstration (CL).
Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48)	5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.	Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 48 hours (Ae0-48).
Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24)	5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.	Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 24 hours (Fe0-24).
Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48)	5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.	Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 48 hours (Fe0-48).
Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24)	5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.	Renal clearance of BI 6727 from the time point 0 to time point 24 hours (CLr,0-24).
Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48)	5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.	Renal clearance of BI 6727 from the time point 0 to time point 48 hours (CLr,0-48).

Trial Locations

Locations (2)

1230.1.32002 Boehringer Ingelheim Investigational Site; 🇧🇪 Brussels, Belgium

1230.1.32001 Boehringer Ingelheim Investigational Site; 🇧🇪 Leuven, Belgium