Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: 5-ALA; Gliadel wafers; Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist; Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist; Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist
Intervention description: 5-ALA is used to generate tumour specific fluorescence as an aid to surgical resection of GBM, prior to the insertion of 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.; 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; 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; 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
Intervention MeSH terms: Carmustine; Aminolevulinic Acid; Levulinic acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult giant cell glioblastoma; adult gliosarcoma; adult glioblastoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as Gliadel wafer and temozolomide, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving
      radiation therapy and temozolomide after surgery and Gliadel wafer may kill any tumor cells
      that remain after surgery.

      PURPOSE: This phase II trial is studying the side effects of fluorescence-guided surgery with
      5-ALA given together with Gliadel wafer, followed by radiation therapy and temozolomide, in
      treating patients with primary glioblastoma.
    

Eligibility criteria:

        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