Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Cisplatin

patient to receive 3-weekly infusion escalating dose of BI 6727 combined to cisplatin

patient to receive 3-weekly infusion escalating dose of BI 6727 combined to carboplatin

Low to high dose (administered every 3 weeks). Depending on the toxicities observed, intermediary dose levels may be added

BI-6727

BI 6727

Boehringer Ingelheim

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.

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

A Phase I Dose Escalation Trial of BI 6727 in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumors

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.

Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle.

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

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 was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria.

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 was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first.

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 common terminology criteria for adverse events (CTCAE) version 3.0

Percentage of participants with serious adverse events (AEs)

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)

Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.

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 pulse rate at last value on treatment

Change from baseline in neutrophils with the maximum value on treatment

Change from baseline in platelets with the maximum value on treatment

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 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).

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).

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)

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).

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)

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 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).

Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V200+Cis75

Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V300+Cis75

Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 100mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V300+Cis100

Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V350+Cis75

Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC4 (area under the curve of 4) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V100+Car4

Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V100+Car5

Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V200+Car5

Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V300+Car5

Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC6 (area under the curve of 6) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V300+Car6

Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V350+Car5

Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 60mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V100+Cis60

Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.

V100+Cis75

Total

Age, Continuous

Sex: Female, Male

Treated set which included all patients who received at least one administration of volasertib and cisplatin or carboplatin.

Boehringer Ingelheim Call Center

Maximum Tolerated Dose

Treated set.

There was one patient in the V300+Car6 group whose DLT data was not evaluable, so only 12 patients had evaluable data.

Percentage of Participants With Dose Limiting Toxicities

Objective Response Rate

Treated set restricted to participants with confirmed objective response.

Duration of Objective Response

Complete response

Partial response

Stable disease

Progressive disease

Non evaluable

No post-baseline tumour assessment

Best Overall Response

Disease Control Rate

Treated set restricted to participants with confirmed disease control.

Duration of Disease Control

Progression-free Survival

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Incidence and Intensity of Adverse Events According to CTCAE Version 3.0

Percentage of Participants With Serious Adverse Events

Percentage of Participants With Significant Adverse Events

Pharmacokinetic (PK) set which included all participants in the treated set with evaluable PK data

Spots Global Cancer Trial Database for BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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