NOA-12: BIBF1120 and R-RT in Glioblastoma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: BIBF 1120
* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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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, α/β=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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF 1120 + reirradiation<br>2 x minimal tolerated dose BIBF 1120 per day in combination with radiotherapy (2 Gy / fraction; 36 Gy in total) | Drug: BIBF 1120<br>* 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.<br>|
| Active Comparator: reirradiation alone<br>radiotherapy (2 Gy / fraction; 36 Gy in total) | Radiation: radiotherapy<br>* 36 Gy, 2 Gy / fraction, 18 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I) |  | day 0, 8, 15 and 17 post-dose during phase I | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability of BIBF1120 |  | Up to 90 days follow-up | 
| Progression-free survival |  | Time from randomization until death or disease progression | 
| Objective response rates (OR) |  | Time from randomization until response | 
| Overall survival |  | Time from randomization until death | 
| Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20 |  | Screening and 6-weekly after radiotherapy | 
| Cognitive function determined by MMSE |  | Screening and 6-weekly after end of radiotherapy |