Phase 1
Completed N=12
Open Dose Escalating Trial to Determine the Maximum Tolerated Dose in Paediatric Patients With Advanced Cancers for Whom no Therapy is Known
leukemia · Neoplasms
Source: ClinicalTrials.gov NCT01971476 ↗
Enrolled (actual)
12
Serious AEs
77.3%
Results posted
Jul 2018
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) — 0; 0; 0; 0 Participants
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) |
0; 0; 0; 0; 2 | — |
| PRIMARY Maximum Tolerated Dose of Volasertib |
300; 200 | — |
| SECONDARY Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI) |
0; 1; 1; 3; 1; 0 | — |
| SECONDARY 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 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations |
0; 0; 1; 2; 1; 0 | — |
| SECONDARY 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 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Event-Free Survival (EFS) [in Leukaemia Patients] |
NA; NA; NA; NA | — |
| SECONDARY Overall Survival (OS) [in Leukaemia Patients] |
NA; NA; NA; NA | — |
| SECONDARY Maximum Measured Concentration (Cmax, Norm) of Volasertib |
5.34; 9.71; 3.60; 2.46; 2.50 | — |
| SECONDARY Trough Concentration (Cpre, 2) of Volasertib |
1.48; 1.13 | — |
| SECONDARY Area Under the Concentration-Time Curve (AUC0-∞, Norm) of Volasertib in Plasma |
41.7; 51.2; 36.4; 28.6; 22.1 | — |
| SECONDARY Half-Life (t1/2) of Volasertib |
102; 130; 54.8; 78.6; 52.7 | — |
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
Data sourced from ClinicalTrials.gov (NCT01971476). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.