Clinical Trial Finder

INCLUSION CRITERIA.i. The patient is reviewed at a specialist neuro-oncology multi-disciplinary team (MDT). ii. Stealth MRI (neuronavigation) will be performed prior to surgery. iii. Imaging is evaluated by a neuro-radiologist and judged to have typical appearances of a primary GBM.iv. Radical resection is judged to be realistic by the neurosurgeons at the MDT (i.e. NICE criteria for the use of Carmustine wafers can be met) v. WHO performance status 0 or 1.vi. Age ≥18.vii. Patient judged by MDT to be fit for standard radical aggressive therapy for GBM (resection followed by RT with concomitant and adjuvant temozolomide) EXCLUSION CRITERIA.i. GBM thought to be transformed low grade or secondary disease.ii. The patient has not been seen by a specialist MDT. iii. There is uncertainty about the radiological diagnosis.iv. 5-ALA or Carmustine wafers is contra-indicated (inc known or suspected allergies to 5-ALA or porphyrins, or acute or chronic types of porphyria) v. Pregnant or lactating women.vi. Known or suspected HIV or other significant infection or comorbidity that would preclude radical aggressive therapy for GBM.vii. Active liver disease (ALT or AST ≥5 x ULRR) viii. Concomitant anti-cancer therapy except steroids.ix. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years.x. Previous brain surgery (including biopsy) or cranial radiotherapy.xi. Platelets <100 x109/L.xii. Mini mental status score <15

OBJECTIVES: Primary.

• - To establish that the combined use of 5-ALA and Gliadel wafers during fluorescence-guided radical brain tumor resection is safe and does not compromise patients with primary glioblastoma from receiving or completing adjuvant standard radiotherapy plus temozolomide.

Secondary.

• - To gather preliminary evidence that the combined use of 5-ALA and Gliadel wafers at surgery has the potential to improve clinical outcome, via measurement of time to clinical progression.

• - To gather preliminary evidence that this regimen at surgery has the potential to improve clinical outcome via measurement of survival at 24 months.

OUTLINE: This is a multicenter study. Gliadel wafers are applied to resection cavity immediately after 5-ALA fluorescence-guided radical brain tumor resection. After recovery from surgery (within 6 weeks of surgery when possible ), patients receive adjuvant chemoradiotherapy comprising standard radiotherapy and temozolomide. Tumor biopsy and blood sample may be collected at time of surgery for retrospective MGMT status analysis. After surgery, patients are followed up at post-surgical visits, during subsequent therapy at routine clinic visits, and at 12, 18, and 24 months. Peer reviewed and funded by Cancer Research UK.

Arms

Experimental: 5-ALA and Gliadel wafers

This is a single arm feasibility study to evaluate the safety and tolerability of combining 2 technologies (5-ALA and Gliadel wafers) in the surgical management of patients with GBM.

Interventions

Drug: - 5-ALA

5-ALA is used to generate tumour specific fluorescence as an aid to surgical resection of GBM, prior to the insertion of Gliadel wafers

Drug: - Gliadel wafers

The implantation of Carmustine Wafers (Gliadel) delivers carmustine- (3-bis 2-chloroethyl 1-1-nitrosourea (BCNU)) directly into the surgical cavity created after tumour resection.

Radiation: - Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist

60Gy in 30 fractions (2Gy per fraction given once daily, five days per week (Monday-Friday) over 6 weeks. Radiotherapy delivered to gross tumour volume with 2-3cm margin. Standard treatment following neurosurgery for glioblastoma

Drug: - Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist

temozolomide given alongside the radiotherapy at 75mg/m2 daily from the first day of radiotherapy, until the last day of radiotherapy, but for no longer than 49 days. Standard treatment following neurosurgery for glioblastoma

Drug: - Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist

Following a 4 week break after contomitant chemo/RT, temozolomide given 150-200mg/m2 TMZ 5/28 days for 6 cycles (dosage increase to 200mg/m2 on second and subsequent cycles dependent on haematological toxicity. Sites should follow local guidelines if different.). TMZ to be given on 5 consecutive days followed by 23 days with no TMZ, per cycle. Standard treatment following neurosurgery and concomitant chemo/RT for glioblastoma