NOA-12: BIBF1120 and R-RT in Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01666600
Recruitment Status : Terminated (Interim Analysis for Feasibility)
First Posted : August 16, 2012
Last Update Posted : November 1, 2017
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Wick, University Hospital Heidelberg

Brief 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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: BIBF 1120 Radiation: radiotherapy Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2012
Actual Primary Completion Date : March 2017
Actual Study Completion Date : September 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BIBF 1120 + reirradiation
2 x minimal tolerated dose BIBF 1120 per day in combination with radiotherapy (2 Gy / fraction; 36 Gy in total)
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.

Active Comparator: reirradiation alone
radiotherapy (2 Gy / fraction; 36 Gy in total)
Radiation: radiotherapy
36 Gy, 2 Gy / fraction, 18 fractions

Primary Outcome Measures :
  1. Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I) [ Time Frame: day 0, 8, 15 and 17 post-dose during phase I ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01666600

University Hospital Heidelberg, Department of Neurooncology
Heidelberg, Baden-Württemberg, Germany, 69120
University Hospital Heidelberg, Department of Pharmacology
Heidelberg, Baden-Württemberg, Germany, 69120
Sponsors and Collaborators
Prof. Dr. Wolfgang Wick

Responsible Party: Prof. Dr. Wolfgang Wick, Professor Dr. med., University Hospital Heidelberg Identifier: NCT01666600     History of Changes
Other Study ID Numbers: NONK-3/NOA-12
First Posted: August 16, 2012    Key Record Dates
Last Update Posted: November 1, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action