Open Dose Escalating Trial to Determine the Maximum Tolerated Dose in Paediatric Patients With Advanced Cancers for Whom no Therapy is Known

NCT01971476 | Completed Phase 1 Results

• 2 other identifiers: 1230.272013-001291-38
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 5

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

Conditions

Leukemia; Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

  This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLTs were defined as drug related Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (haematological and nonhaematological) Adverse Events (AEs) with the exception of a) Reduced blood cell count (any grade) without associated clinical complications qualifying for DLT. b) Febrile neutropenia Grade 3. c) Infection Grade 3 with neutrophil count \<1000/mm3. d) Uric acid Grade ≥3. e) Nausea, vomiting and/or diarrhoea managed by adequate therapy (i.e. recovery to CTCAE Grade ≤2).

  Up to 14 days.

• Maximum Tolerated Dose of Volasertib

  This outcome measure presents MTD of Volasertib. The MTD was defined as the highest dose level at which DLTs were reported in not more than 1 in 6 evaluable patients during Cycle 1.

  Up to 14 days.

Secondary Outcomes (10)

• Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI)

  Up to 879 days.

• 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

  Up to 879 days.

• The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations

  Up to 879 days.

• 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

  Up to 849 days.

• Event-Free Survival (EFS) [in Leukaemia Patients]

  Up to 849 days.

Study Arms (1)

All patients

EXPERIMENTAL

Volasertib will be administered as intravenous infusion

Drug: volasertib

Interventions

volasertib DRUG

intravenous administration on day 1of a treatment course

All patients

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (5)

UNIV UZ Gent

Ghent, 9000, Belgium

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

INS Curie

Paris, 75248, France

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

Osp. Pediatrico Bambin Gesù

Roma, 00165, Italy

Location

MeSH Terms

Conditions

Leukemia; Neoplasms

Interventions

BI 6727

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 29, 2013
• Study Start: October 22, 2013
• Primary Completion: June 1, 2015
• Study Completion: January 27, 2017
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2017-10

Locations

DE (1); BE (1); IT (1); CZ (1); FR (1)