Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma

University College London (UCL)

Status and phase: Completed; Phase 2

Conditions: Glioblastoma

Treatments: Drug: 5-ALA; Drug: Gliadel wafers; Drug: Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist; Radiation: Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist; Drug: Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist

Study type: Interventional

Funder types: Other

Identifiers

NCT01310868

CDR0000696316

CRUK-UCL-09-0398 (Other Grant/Funding Number)

2010-022496-66 (EudraCT Number)

09/0398 (Other Identifier)

10/H0304/100 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 59 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 1 patient group

5-ALA and Gliadel wafers

Experimental group

Description:

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.

Treatment:

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

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

Drug: Gliadel wafers

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

Drug: 5-ALA