Clinical trial NCT02273388: BI 6727 Administered Intravenously Every 3 Weeks in Patients With Solid Tumours
Official title: An Open Phase I Single Dose Escalation Study of BI 6727 Administered Intravenously in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-24
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
2. Age 18 years or older
3. Written informed consent consistent with ICH-GCP and local legislation
4. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ¿ 2
5. Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies (except alopecia)

   The 18 additional patients recruited at the MTD must also meet the following criterion:
6. Measurable tumour deposits (RECIST) by one or more techniques (CT, MRI)

Exclusion criteria:

1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
2. Pregnancy or breastfeeding
3. Active infectious disease or known chronic Hepatitis B/Hepatitis C infection
4. Clinical evidence of active brain or leptomeningeal disease during the past 12 months
5. Second malignancy currently requiring active therapy
6. Absolute neutrophil count less than 1500 / mm3
7. Platelet count less than 100 000 / mm3
8. Bilirubin greater than 1.5 mg / dl (\> 26 ¿mol / L, SI unit equivalent)
9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
10. Serum creatinine greater than 1.5 mg / dl (\> 132 ¿mol / L, SI unit equivalent)
11. Known history of relevant QT-prolongation, e.g. long QT-syndrome
12. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
13. Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
14. Chemo-, radio or immunotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
15. Patients unable to comply with the protocol
16. Active alcohol or drug abuse

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 21 days (first treatment course).
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first drug administration until last drug administration plus 21 days, up to 835 days.
measure: Number of Participants With Clinically Relevant Abnormalities
timeFrame: From baseline to the last value on treatment, up to 814 days.
measure: Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score
timeFrame: At baseline and at end of treatment (up to 814 days).
measure: Electrocardiogram (ECG) - QTcF Change From Baseline
timeFrame: 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.
measure: Vital Signs - Blood Pressure
timeFrame: At baseline.
measure: Vital Signs - Pulse Rate
timeFrame: At baseline.
measure: Number of Participants With Unconfirmed Best Overall Response
timeFrame: Up to 814 days.
measure: Number of Participants With Progression
timeFrame: Up to 814 days.
measure: Maximum Concentration of BI 6727 in Plasma (Cmax)
timeFrame: 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).
measure: Time From Dosing to Maximum Concentration (Tmax)
timeFrame: 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).
measure: Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
timeFrame: 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).
measure: 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)
timeFrame: 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).
measure: Terminal Rate Constant in Plasma (λz)
timeFrame: 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).
measure: Terminal Half-life of the Analyte in Plasma (t1/2)
timeFrame: 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).
measure: Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT)
timeFrame: 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).
measure: Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL)
timeFrame: 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).
measure: Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)
timeFrame: 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).
measure: Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz)
timeFrame: 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).
measure: Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
measure: Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
measure: Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
measure: Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
measure: Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
measure: Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48)
timeFrame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: 1230.1.32002 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1230.1.32001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: