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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01310868
Recruitment Status : Completed
First Posted : March 9, 2011
Results First Posted : August 14, 2017
Last Update Posted : October 5, 2017
Information provided by (Responsible Party):
University College, London

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.

Condition or disease Intervention/treatment Phase
Glioblastoma 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 Phase 2

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2011
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Arm Intervention/treatment
Experimental: 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.
Drug: 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
Other Names:
  • Amino-levulinic Acid
  • Gliolan

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.
Other Names:
  • Carmustine wafers
  • polifeprosan 20 with carmustine implant

Radiation: 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

Drug: 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

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

Primary Outcome Measures :
  1. Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide [ Time Frame: 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 :
  1. 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 ]
  2. Survival at 24 Months [ Time Frame: from the date of surgery to 24 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


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)


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01310868

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United Kingdom
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
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
Sponsors and Collaborators
University College, London
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Principal Investigator: Colin Watts Cambridge University Hospitals NHS Foundation Trust
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Responsible Party: University College, London Identifier: NCT01310868    
Other Study ID Numbers: CDR0000696316
CRUK-UCL-09-0398 ( Other Grant/Funding Number: Cancer Research UK and Samantha Dixon Brain Tumour Trust )
2010-022496-66 ( EudraCT Number )
09/0398 ( Other Identifier: University College London )
10/H0304/100 ( Other Identifier: NRES Committee East of England - Cambridge East )
First Posted: March 9, 2011    Key Record Dates
Results First Posted: August 14, 2017
Last Update Posted: October 5, 2017
Last Verified: September 2017
Keywords provided by University College, London:
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aminolevulinic Acid
Levulinic acid
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Photosensitizing Agents
Dermatologic Agents