Clinical trial NCT01310868: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2011-03-09
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide
timeFrame: Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)
Secondary outcomes:
measure: Time to Clinical Progression
timeFrame: 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
measure: Survival at 24 Months
timeFrame: from the date of surgery to 24 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: Lancashire
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Southern General Hospital
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: University College London Hospital/ National Hospital for Neurology and Neurosurgery
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Colin Watts
role: PRINCIPAL_INVESTIGATOR
References: