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

Phase 2

Completed

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

Brief 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.

Detailed 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
5-ALA and Gliadel wafers	Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist	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.
5-ALA and Gliadel wafers	Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist	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.
5-ALA and Gliadel wafers	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.
5-ALA and Gliadel wafers	Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist	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.
5-ALA and Gliadel wafers	5-ALA	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.

Primary Outcome Measures

Name	Time	Method
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide	Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)	Procedure compliance: Proportion of 5-ALA resected patients who received Carmustine wafer implants (e.g to take into account rates of patients who did not receive Carmustine wafer implants due to 1) ventricular breach, 2) inaccurate peri-operative diagnosis, 3) intra-operative surgical decision) * Post-operative complication rate: Proportion of patients with a new post-operative deficit or surgical complication (wound infection, CSF leakage, intracranial hypertension) * No. of patients with chemoRT delay (i.e number who do not begin chemoRT 6 weeks after surgery) due to surgical complications\* * No. of patients failing to start chemoRT due to surgical complications rather than tumour progression * No. of patients failing to complete chemoRT without interruption (RT with concomitant chemotherapy, and RT with concomitant plus adjuvant chemotherapy) * Proportion of patients with a lower WHO performance status after surgery with Carmustine wafers (at first post-operative clinic visit)

Secondary Outcome Measures

Name	Time	Method
Time to Clinical Progression	from the date of surgery to the date of the first MRI scan fitting the criteria for progression, or the date the clinical detrioration or death was first reported
Survival at 24 Months	from the date of surgery to 24 months

Locations (10): Royal Preston Hospital
🇬🇧
Preston, Lancashire, United Kingdom
Leeds General Infirmary
🇬🇧
Leeds, United Kingdom
Ninewells Hospital
🇬🇧
Dundee, United Kingdom
Southern General Hospital
🇬🇧
Glasgow, United Kingdom
Addenbrooke's Hospital
🇬🇧
Cambridge, England, United Kingdom
The Walton Centre
🇬🇧
Liverpool, United Kingdom
University College London Hospital/ National Hospital for Neurology and Neurosurgery
🇬🇧
London, United Kingdom
King's College Hospital
🇬🇧
London, United Kingdom
Hull Royal Infirmary
🇬🇧
Hull, United Kingdom
Royal Hallamshire Hospital
🇬🇧
Sheffield, United Kingdom