Back to resultsGliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
Primary Purpose
Glioblastoma
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
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
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring adult giant cell glioblastoma, adult gliosarcoma, adult 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
Sites / Locations
- Addenbrooke's Hospital
- Royal Preston Hospital
- Ninewells Hospital
- Southern General Hospital
- Hull Royal Infirmary
- Leeds General Infirmary
- The Walton Centre
- King's College Hospital
- University College London Hospital/ National Hospital for Neurology and Neurosurgery
- Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
5-ALA and Gliadel wafers
Arm 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.
Outcomes
Primary Outcome Measures
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide
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
Time to Clinical Progression
Survival at 24 Months
Full Information
NCT ID
NCT01310868
First Posted
March 5, 2011
Last Updated
September 6, 2017
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT01310868
Brief Title
Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
Official Title
An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) With Carmustine Wafers (Gliadel) in the Surgical Management of Primary Glioblastoma (GALA-5 Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5-ALA and Gliadel wafers
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
5-ALA
Other Intervention Name(s)
Amino-levulinic Acid, Gliolan
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
Intervention Type
Drug
Intervention Name(s)
Gliadel wafers
Other Intervention Name(s)
Carmustine wafers, polifeprosan 20 with carmustine implant
Intervention Description
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
Radiation
Intervention Name(s)
Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist
Intervention Description
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
Drug
Intervention Name(s)
Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist
Intervention Description
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
Intervention Name(s)
Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist
Intervention Description
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
Primary Outcome Measure Information:
Title
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide
Description
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)
Time Frame
Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)
Secondary Outcome Measure Information:
Title
Time to Clinical Progression
Time Frame
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
Title
Survival at 24 Months
Time Frame
from the date of surgery to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colin Watts
Organizational Affiliation
Cambridge University Hospitals NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
State/Province
Lancashire
Country
United Kingdom
Facility Name
Ninewells Hospital
City
Dundee
Country
United Kingdom
Facility Name
Southern General Hospital
City
Glasgow
Country
United Kingdom
Facility Name
Hull Royal Infirmary
City
Hull
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
The Walton Centre
City
Liverpool
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
University College London Hospital/ National Hospital for Neurology and Neurosurgery
City
London
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
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