NOA-12: BIBF1120 and R-RT in Glioblastoma

NCT01666600 | Terminated Phase 1 DMC

• 1 other identifier: NONK-3/NOA-12
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

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.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I)

  day 0, 8, 15 and 17 post-dose during phase I

Secondary Outcomes (6)

• 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

Study Arms (2)

BIBF 1120 + reirradiation

EXPERIMENTAL

2 x minimal tolerated dose BIBF 1120 per day in combination with radiotherapy (2 Gy / fraction; 36 Gy in total)

Drug: BIBF 1120

reirradiation alone

ACTIVE COMPARATOR

radiotherapy (2 Gy / fraction; 36 Gy in total)

Radiation: radiotherapy

Interventions

BIBF 1120 DRUG

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.

BIBF 1120 + reirradiation

radiotherapy RADIATION

36 Gy, 2 Gy / fraction, 18 fractions

reirradiation alone

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Prof. Dr. Wolfgang Wick: lead

Study Sites (2)

University Hospital Heidelberg, Department of Neurooncology

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Hospital Heidelberg, Department of Pharmacology

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

nintedanib; Radiotherapy

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Dr. med.

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: August 16, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: September 1, 2017
• Last Updated: November 1, 2017

Record last verified: 2017-10

Locations

DE (2)