Dovitinib (TKI258) in the Treatment of Patients With Relapsed Glioblastoma

NCT01972750 | Unknown Phase 1 DMC

• 1 other identifier: CTKI258ADE02T
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

In this study with a modified 3+3 dose finding design, a safe and tolerable dose of TKI258 in patients with relapsed glioblastoma should be established.

Conditions

First or Second Recurrence of Glioblastoma

Keywords

glioblastoma; recurrence

Outcome Measures

Primary Outcomes (1)

• safety and tolerance

  The primary endpoint is safety and tolerance and will be based on the frequency of DLTs.

  2 cycles of Dovitinib application (2 months)

Secondary Outcomes (5)

• Tumor response (CR, PR)

  14 months

• Overall safety

  14 months

• Disease Control Rate (CR + PR + SD)

  14 months

• Progression free survival rate

  14 months

• Quality of life

  14 months

Study Arms (1)

Dovitinib

EXPERIMENTAL

IMP: Dovitinib (TKI258) Manufacturer: Novartis Dose: 500 mg/day Mode of application: orally Duration of treatment: 5 days / week (5 days on / 2 days off) of a 28-days cycle until progression of disease

Drug: Dovitinib

Interventions

Dovitinib DRUG

daily oral intake of capsule

Also known as: TKI258

Dovitinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects, male or female, Age ≥ 18 years
• First or second recurrence of histologically confirmed glioblastoma
• A Performance Scale of Karnofsky \> 60%, ECOG ≤ 2 or WHO \< 2
• Patients must have been on no steroids or a stable dose of steroids for at least 5 days before the baseline MRI scan
• Prior treatment with radiotherapy and temozolomide and a maximum of two prior chemotherapies is permitted
• No radiotherapy within the 4 weeks prior to the diagnosis of progres-sion.
• Patient may have been operated for recurrence. If operated residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence a post-surgery. MRI should be available within 48 hours following surgery
• Adequate organ function as described below:
• Adequate bone marrow reserve: ANC ≥ 1.5 x 10\^9/L, Platelets ≥ 100 x 10\^9/L, Haemoglobin \> 9 g/dL
• Adequate liver function: Total bilirubin ≤ 1.5 x ULN (excepted for patients with Gilbert's syndrome), ALT and AST ≤ 3.0 x ULN
• Adequate renal function: Creatinine ≤ 1.5 x ULN
• No core biopsy or other minor surgical procedure within 7 days prior to randomization. Placement of a central vascular access device (CVAD) if performed at least 5 days prior to study treatment administration is allowed.
• Subjects with the ability to follow study instructions and likely to attend and complete all required visits

You may not qualify if:

• Subjects not able to give consent
• Subject without legal capacity who is unable to understand the nature, scope, significance and consequences of this clinical trial
• Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure
• Simultaneously participation in another clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
• Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the trial results, or may interfere with the subject's participation in this clinical trial
• Known or persistent abuse of medication, drugs or alcohol
• Evidence of current/active intratumor hemorrhage by MRI
• More than two relapses
• Elongation of corrected QT-time (QTc) \> 450 ms (male patients) and ≥ 460 ms (female patients), respectively
• Patients with any clinically significant medical or surgical condition which, according to investigators´ discretion, should preclude participation - i.e. severe renal disease, severe pancreatic disease, active or uncontrolled infection, uncontrolled diabetes, active or chronic liver disease (cirrhosis, chronic active hepatitis or chronic persistent hepatitis) - hepatitis B or C virus carriers with normal liver function tests, can be included.
• Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmi-as
• Bradycardia (\<60/min): i) Clinically significant resting bradycardia (=\> 40/min) with syncopes or chronotropic incompetence or ii) asymptomatic bradycardia with a heart rate \< 40/min and/or paus-es in ventricular rate \> 3 s
• LVEF assessed by 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (which ever is higher)
• Any of the following within 6 months prior to starting TKI258:

Sponsors & Collaborators

• PD Dr. Martin Glas: lead

Study Sites (1)

Department of Neurology and Center of Integrated Oncology, University Hospital Bonn

Bonn, 53105, Germany

Location

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Martin Glas, MD

  Neurooncology, University Hospital Bonn

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator and Sponsor delegated person

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 19, 2016

Record last verified: 2016-04

Locations

DE (1)