GlioblastomaPhase 2NCT01310868
Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
A Phase 2 study testing 5-ALA, Gliadel wafers and Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist in people with Glioblastoma, run by University College, London at 10 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- 5-ALA, Gliadel wafers and Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- May 2011to Mar 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is reviewed at a specialist neuro-oncology multi-disciplinary team (MDT).
- Stealth MRI (neuronavigation) will be performed prior to surgery.
- Imaging is evaluated by a neuro-radiologist and judged to have typical appearances of a primary GBM
- 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)
- WHO performance status 0 or 1
- Age ≥18
- Patient judged by MDT to be fit for standard radical aggressive therapy for GBM (resection followed by RT with concomitant and adjuvant temozolomide)
Who cannot join
- GBM thought to be transformed low grade or secondary disease
- The patient has not been seen by a specialist MDT.
- There is uncertainty about the radiological diagnosis
- 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)
- Pregnant or lactating women
- Known or suspected HIV or other significant infection or comorbidity that would preclude radical aggressive therapy for GBM
Show all 12Show fewer
- Active liver disease (ALT or AST ≥5 x ULRR)
- Concomitant anti-cancer therapy except steroids
- History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years
- Previous brain surgery (including biopsy) or cranial radiotherapy
- Platelets <100 x109/L
- Mini mental status score <15
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Ninewells Hospital
Dundee
Southern General Hospital
Glasgow
Hull Royal Infirmary
Hull
Leeds General Infirmary
Leeds
The Walton Centre
Liverpool
King's College Hospital
London
University College London Hospital/ National Hospital for Neurology and Neurosurgery
London
Royal Preston Hospital
Preston, Lancashire
Royal Hallamshire Hospital
Sheffield
About this study
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)
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.
Read the 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
- Being tested
- 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
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-ALADrug
Also called Amino-levulinic Acid, Gliolan
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 wafersDrug
Also called Carmustine wafers, polifeprosan 20 with carmustine implant
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-oncologistRadiation
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-oncologistDrug
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-oncologistDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 5-ALA and Gliadel wafers | Experimental | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)
Secondary outcomes (2)
Time to Clinical Progression
Measured: 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
Measured: from the date of surgery to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Colin Watts, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310868
- Sponsor's protocol ID
- CDR0000696316
- Other IDs
- CRUK-UCL-09-0398, 2010-022496-66, 09/0398, 10/H0304/100
- Status last verified
- Sep 2017
- First submitted
- 5 Mar 2011
- Last updated
- 5 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01310868
- Acronym / sponsor ID
- CDR0000696316
- Conditions
- Glioblastoma
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 9 Mar 2011 (estimated)
- Results
- Posted 14 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-ALA and Gliadel wafers | Experimental | 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-oncologistThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The patient is reviewed at a specialist neuro-oncology multi-disciplinary team (MDT).
- Stealth MRI (neuronavigation) will be performed prior to surgery.
- Imaging is evaluated by a neuro-radiologist and judged to have typical appearances of a primary GBM
- 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)
- WHO performance status 0 or 1
Key exclusion criteria (12 listed)
- GBM thought to be transformed low grade or secondary disease
- The patient has not been seen by a specialist MDT.
- There is uncertainty about the radiological diagnosis
- 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)
- Pregnant or lactating women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-ALAAlso: Amino-levulinic Acid, Gliolan5-ALA is used to generate tumour specific fluorescence as an aid to surgical resection of GBM, prior to the insertion of Gliadel wafers | Drug | 5-ALA and Gliadel wafers |
| Gliadel wafersAlso: Carmustine wafers, polifeprosan 20 with carmustine implantThe implantation of Carmustine Wafers (Gliadel) delivers carmustine- (3-bis 2-chloroethyl 1-1-nitrosourea (BCNU)) directly into the surgical cavity created after tumour resection. | Drug | 5-ALA and Gliadel wafers |
| Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist60Gy 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 | Radiation | 5-ALA and Gliadel wafers |
| Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologisttemozolomide 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 | 5-ALA and Gliadel wafers |
| Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologistFollowing 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 | Drug | 5-ALA and Gliadel wafers |
Primary outcome
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)
2 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colin Watts principal investigator
Cambridge University Hospitals NHS Foundation Trust
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-ALA, Gliadel wafers and Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist in people with Glioblastoma, run by University College, London at 10 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.