BRIOChe: A trial looking at re-irradiation and chemotherapy in patients with recurrent glioblastoma.

Phase 1

Active, not recruiting

Conditions: Recurrent Glioblastoma
MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-004053-91-GB

Lead Sponsor: niversity of Leeds

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 70

Inclusion Criteria

• Histologically proven diagnosis of GBM with consistent molecular pathology, based on original pathology.
• First recurrence of GBM, with contrast enhancing disease, following primary treatment (or following surgery alone for first recurrence of GBM; i.e. no previous systemic therapy or re-irradiation for recurrence permitted).
• The MRI scan that reveals recurrence must be reviewed by the local multi-disciplinary meeting, including agreement of a Consultant Neuro-Radiologist that imaging changes are in keeping with recurrence and not pseudo-progression.
• Randomisation must be performed within 21 days of the MRI that confirms recurrence. Outside of 21 days, an updated MRI is required to confirm eligibility and serve as a contemporaneous baseline scan to assess response to further treatment. Please see section 9 Assessments for further details for achieving this.
• =6 months since completion of primary radiotherapy (where the interval since radiotherapy completion is 5 months and 2 weeks or greater, this may be rounded up to 6 months and the patient included in the trial).
• Prior history of standard dose, conventionally fractionated CNS radiotherapy (i.e. 54-60Gy in 28-33 fractions).
• As a minimum patients will have completed at least two weeks of temozolomide, concurrent with their original radiotherapy.
• Up to and including three enhancing lesions:
- In cases of a single recurrent enhancing lesion:
-predicted re-irradiation GTV<75cm3 (based on diagnostic MR imaging and on maximum diameters of enhancing disease in all 3 planes, calculated from 4/3p x ½ x diameter 1 x ½ x diameter 2 x ½ x diameter 3, and
-maximum diameter of enhancing disease must be =6cm. In cases where there is circumferential enhancement around a cavity, such that the cavity and enhancing disease will be included in the GTV, then the maximum diameter of enhancing disease and cavity must be =6cm.
-In cases of multiple (i.e. two or three) discrete recurrent enhancing lesions:
-the total (i.e. combined) predicted re-irradiation GTV must be <50cm3 and lesions must be clustered in a similar brain region such that PTVs are anticipated to be adjacent or overlapping, and
-maximum diameter of combined enhancing disease, across all enhancing lesions (including any gaps between), must be =6cm.
• Karnofsky Performance Status 70+
• Adequate hematologic, renal, and hepatic function (absolute neutrophil count, =1.5 x 109/L; platelet count, =100 x 109/L; White cell count =3.0 x 109/L; haemoglobin =10g/L (may be corrected by transfusion); serum creatinine clearance (measured or estimated) =30ml/min; total serum bilirubin level <1.5 times ULN; and ALT <5 times ULN) within 14 days prior to randomisation. (Dose modifications may still be required based on these parameters). Lymphopaenia is not a contra-indication to trial entry.
• Patients who have had surgery for first recurrence may also be included provided there is residual enhancing disease on the immediate post-operative MRI or if enhancing disease develops on subsequent follow-up imaging, provided no prior systemic therapy or re-irradiation for recurrence has been given. As above, this MRI must be reviewed within the local multi-disciplinary meeting, with agreement of a Consultant Neuro-Radiologist that the imaging changes are in keeping with residual or new enhancing disease. Randomisation must be performed within 21 days of the MRI that confirms re

Exclusion Criteria

• Pregnant (positive pregnancy test) or lactating.
• Critical normal brain structures treated above usual tolerance during initial radiotherapy (i.e. based on 30 fractions initial treatment, >55Gy delivered to 1% or 0.1cm3 of optic nerve or chiasm or >55Gy delivered to >1cm3 of brainstem or >57Gy delivered to >0.1cm3 of brainstem or >50Gy to 1% or 0.1cm3 of globes).
• Recurrence with leptomeningeal disease or only leptomeningeal disease.
• Recurrence defined by non-enhancing disease only.
• More than three enhancing lesions present on MRI or multi-focal recurrence.
• IDH1/2 mutant tumours on original pathology (to avoid unbalance between arms).
• GBM with known features of PXA, BRAF mutations or 1p19q co-deletion (on original pathology or updated pathology if available)
• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of one year.
• Severe active co-morbidity making patient unsuitable for chemotherapy or re-irradiation (e.g. uncontrolled diabetes, uncontrolled hypertension).
• Prior allergic reaction to nitrosoureas.
• Coeliac disease.
• Any recognised genetic syndrome causing sensitivity to radiotherapy.
• Patient unwilling/ unable to attend for follow up in the radiotherapy centre.
• Contraindication to MRI or gadolinium.
• Previous radiotherapy dose distribution unavailable.
• Previous systemic therapy or re-irradiation for recurrent GBM.