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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|ClinicalTrials.gov Identifier: NCT01310868|
Recruitment Status : Completed
First Posted : March 9, 2011
Results First Posted : August 14, 2017
Last Update Posted : October 5, 2017
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|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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.
5-ALA is used to generate tumour specific fluorescence as an aid to surgical resection of GBM, prior to the insertion of Gliadel wafers
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.
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
- 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)
- 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 ]
- Survival at 24 Months [ Time Frame: from the date of surgery to 24 months ]
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 ClinicalTrials.gov identifier (NCT number): NCT01310868
|Cambridge, England, United Kingdom, CB2 2QQ|
|Royal Preston Hospital|
|Preston, Lancashire, United Kingdom|
|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|
|Principal Investigator:||Colin Watts||Cambridge University Hospitals NHS Foundation Trust|