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

NCT ID: NCT01310868

Last Updated: 2017-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-03-31

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

5-ALA

Intervention Type: DRUG

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

Gliadel wafers

Intervention Type: DRUG

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.

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

Intervention Type: RADIATION

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

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

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

Intervention Type: RADIATION

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Amino-levulinic Acid; Gliolan; Carmustine wafers; polifeprosan 20 with carmustine implant

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Colin Watts

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Locations

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Ninewells Hospital

Dundee, , United Kingdom

Southern General Hospital

Glasgow, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

Leeds General Infirmary

Leeds, , United Kingdom

The Walton Centre

Liverpool, , United Kingdom

King's College Hospital

London, , United Kingdom

University College London Hospital/ National Hospital for Neurology and Neurosurgery

London, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-UCL-09-0398

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2010-022496-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

09/0398

Identifier Type: OTHER

Identifier Source: secondary_id

10/H0304/100

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000696316

Identifier Type: -

Identifier Source: org_study_id