Clinical trial NCT01971476: Open Dose Escalating Trial to Determine the Maximum Tolerated Dose in Paediatric Patients With Advanced Cancers for Whom no Therapy is Known
Official title: Open, Non-controlled, Dose Escalating Phase I Trial to Evaluate the Pharmacokinetics, Pharmacodynamics, Tolerability and Toxicity of Volasertib in Paediatric Patients From 2 Years to Less Than 18 Years of Age With Acute Leukaemia or Advanced Solid Tumour, for Whom no Effective Treatment is Known
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-10-29
Enrollment: 22
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The present trial will be performed according to an open design to determine the maximum tolerable dose (MTD) by evaluation of dose-limiting toxicity (DLT) of volasertib in paediatric leukaemia and solid tumours in the age group 2 to less than 12 and 12 to less than 18 years. A further objective is to collect data on safety, tolerability, toxicity, efficacy (preliminary activity), pharmacokinetics and pharmacodynamics of volasertib in paediatric cancer patients


Eligibility criteria: Inclusion criteria:

* paediatric patients with leukaemia or advanced solid tumours including lymphomas (age 2 - less than 18 years) for whom no further treatment is known
* Lansky score \> 60 for children 2 to less than 12 years
* Karnofsky score \> 60 for children aged 12 or older
* life expectancy of at least 6 weeks as judged by the investigator
* parents or legal guardians have given written informed consent and informed assent suitable for the respective age group obtained

Exclusion criteria:

* patient eligible for other anti-leukaemic therapy with curative intent or effective therapy known for solid tumour therapy
* presence of cardiac disease (LVEF by echocardiography less than 25 %)
* symptomatic Central Nervous System involvement of the malignant disease
* primary CNS tumour
* inadequate lab parameters
* inadequate venous access
* QTc prolongation
* pregnancy, breastfeeding
* other diseases or CTs that might interfere with evaluation of safety

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
timeFrame: Up to 14 days.
measure: Maximum Tolerated Dose of Volasertib
timeFrame: Up to 14 days.
Secondary outcomes:
measure: Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI)
timeFrame: Up to 879 days.
measure: Number of Patients With Clinically Relevant Laboratory Value Changes of Calcium (Hyper- and/or Hypocalcaemia) as Judged by the Investigator and Reported as AEs, CTCAE Grade ≥3
timeFrame: Up to 879 days.
measure: The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations
timeFrame: Up to 879 days.
measure: Best Overall Response [in Leukaemia Patients]: (Complete Remission (CR)), CR With Incomplete Neutrophil or Platelet Recovery (CRi), Partial Remission (PR), Stable Disease (SD), Progressive Disease (PD) and Death in Aplasia
timeFrame: Up to 849 days.
measure: Event-Free Survival (EFS) [in Leukaemia Patients]
timeFrame: Up to 849 days.
measure: Overall Survival (OS) [in Leukaemia Patients]
timeFrame: Up to 849 days.
measure: Maximum Measured Concentration (Cmax, Norm) of Volasertib
timeFrame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
measure: Trough Concentration (Cpre, 2) of Volasertib
timeFrame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
measure: Area Under the Concentration-Time Curve (AUC0-∞, Norm) of Volasertib in Plasma
timeFrame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
measure: Half-Life (t1/2) of Volasertib
timeFrame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Prague
country: Czechia
facility: University Hospital Motol
city: Paris
country: France
facility: INS Curie
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Roma
country: Italy
facility: Osp. Pediatrico Bambin Gesù
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: