NOA-12: BIBF1120 and R-RT in Glioblastoma

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase I/II, Randomized, Open-label, Multi-centre Study of BIBF1120 + Reirradiation (R-RT) Versus Reirradiation in the Treatment of Patients With First or Second Progression of Glioblastoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01666600
• Other study ID #: NONK-3/NOA-12
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: July 12, 2012
• Last updated: October 30, 2017
• Start date: August 2012
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with glioblastoma at first or second progression who have failed standard treatment that must have included radiochemotherapy with temozolomide and who are a candidate for a reirradiation can be included into the trial. In the phase I part the minimal tolerated dose (MTD)of BIBF 1120 in combination with radiotherapy will be investigated. Subjects in phase II will be randomised to receive reirradiation alone or reirradiation + 2 x MTD BIBF1120.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: September 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female patients with a recurrence / progression of glioblastoma either not being eligible for tumour resection or having macroscopic residual tumour after resection of the recurrence

• Diagnosis of glioblastoma must be proven histologically and progress must be documented by MRI. MRI images must not be older than 2 weeks before first dosing/start of RT

• Not more than two prior therapy regimens including one or two resections, one or two chemotherapies (one temozolomide containing concomitant to radiotherapy) and one radiotherapy (RT) for the brain tumour

• Previous irradiation therapy of the primary tumour with a maximal dose of 60 Gy; at least 8 months since the end of preirradiation

• Candidate for reirradiation with recurrent tumour visible on MRIT1 (Gd) and with the largest diameter measuring 1 cm to 5 cm

• Informed consent

• Age = 18 years, smoking or non-smoking, of any ethnic origin

• Karnofsky performance index (KPI) = 60%

• Neutrophile counts > 1500/µl / Platelet counts > 80.000/µl /Haemoglobin > 10 g/dl / Serum creatinine < 1.5-fold upper normal range / Bilirubin, AST or ALT < 2,5-fold upper normal range unless attributed to anticonvulsants / Alkaline phosphatase < 2,5-fold upper normal range

• Adequate contraception

• If on steroids, stable or decreasing treatment with steroids within 5 days before treatment start

Exclusion Criteria:

• More than one RT of brain, prior first radiotherapy with more than 60 Gy

• Cumulative total dose on the optical chiasm >54 Gy for 2 Gy/fraction, a/ß=2

• Prior treatment with bevacizumab, iodine seeds and/or brachytherapy

• Unable to undergo MRI

• Past medical history of diseases with poor prognosis according to the judgement of the Investigator, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation

• HIV or hepatitis infection

• Pregnancy or breast feeding

• Treatment within any other clinical trial parallel to the treatment phase of the current study or within 30 days before inclusion

• Known coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure (NYHA class III - IV)

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• BIBF 1120
BIBF 1120 is given as 2 x minimal tolerated dose per day as long as as a clinical benefit is considered by the treating physician.

Radiation:
• radiotherapy
36 Gy, 2 Gy / fraction, 18 fractions

Locations

Country	Name	City	State
Germany	University Hospital Heidelberg, Department of Neurooncology	Heidelberg	Baden-Württemberg
Germany	University Hospital Heidelberg, Department of Pharmacology	Heidelberg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
Prof. Dr. Wolfgang Wick

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I)		day 0, 8, 15 and 17 post-dose during phase I
Secondary	Number of participants with adverse events as a measure of safety and tolerability of BIBF1120		Up to 90 days follow-up
Secondary	Progression-free survival		Time from randomization until death or disease progression
Secondary	Objective response rates (OR)		Time from randomization until response
Secondary	Overall survival		Time from randomization until death
Secondary	Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20		Screening and 6-weekly after radiotherapy
Secondary	Cognitive function determined by MMSE		Screening and 6-weekly after end of radiotherapy