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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

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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
Sponsor:
Information provided by (Responsible Party):
University College, London

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Interventions 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
Enrollment 59

Recruitment Details  
Pre-assignment Details Study entry was based on imaging that has been judged to have typical appearances of a primary glioblastoma multiforme (GBM). Patients would have neurosurgery and GBM would be confirmed peri/post-operatively. If not GBM patients OR wafers+ 5-ala not administered then remain in the trial for follow up but were not included in the final analysis.
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

Period Title: Overall Study
Started 72
Completed 59
Not Completed 13
Reason Not Completed
Do not have histologically confirmed GBM             13
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

Overall Number of Baseline Participants 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
<=18 years
0
   0.0%
Between 18 and 65 years
54
  75.0%
>=65 years
18
  25.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
Female
23
  31.9%
Male
49
  68.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 72 participants
72
1.Primary Outcome
Title Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
of 72 patients recruited, 62 received 5-ALA and carmustine wafers. Of these 62 patients, 59 were found to be eligible and included in the final analysis
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

Overall Number of Participants Analyzed 72
Measure Type: Count of Participants
Unit of Measure: Participants
5-ALA resected patients receiving carmustine wafer Number Analyzed 72 participants
62
  86.1%
No. patients with post-op complications Number Analyzed 59 participants
9
  15.3%
No. Patients with chemoRT delay Number Analyzed 59 participants
6
  10.2%
No. pts failing to complete uninterrupted chemoRT Number Analyzed 59 participants
45
  76.3%
no. pts w decr perform status after 5ala/carmustin Number Analyzed 59 participants
27
  45.8%
no. pts not starting chemoRT due to surgical comp Number Analyzed 59 participants
2
   3.4%
2.Secondary Outcome
Title Time to Clinical Progression
Hide Description [Not Specified]
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients receiving 5-ala and carmustine wafers during surgical resection for glioblastoma multiforme that was confirmed peri/post-operatively
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

Overall Number of Participants Analyzed 59
Median (95% Confidence Interval)
Unit of Measure: months
9.5
(7.5 to 9.8)
3.Secondary Outcome
Title Survival at 24 Months
Hide Description [Not Specified]
Time Frame from the date of surgery to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients receiving 5-ala and carmustine wafers during surgical resection for glioblastoma multiforme that was confirmed peri/post-operatively
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

Overall Number of Participants Analyzed 59
Median (95% Confidence Interval)
Unit of Measure: months
15
(11.9 to 17.3)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 5-ALA and Gliadel Wafers
Hide Arm/Group 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.

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

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.

All-Cause Mortality
5-ALA and Gliadel Wafers
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
5-ALA and Gliadel Wafers
Affected / at Risk (%)
Total   26/59 (44.07%) 
Eye disorders   
retinal detachment   1/59 (1.69%) 
Gastrointestinal disorders   
colonic perforation   1/59 (1.69%) 
other - bowel perforation   1/59 (1.69%) 
intra-abdomial hemorrhage   1/59 (1.69%) 
nausea   1/59 (1.69%) 
vomiting   1/59 (1.69%) 
General disorders   
fever   1/59 (1.69%) 
Infections and infestations   
infection - cerebral abscess   1/59 (1.69%) 
infections other (not specified)   2/59 (3.39%) 
sepsis   2/59 (3.39%) 
urinary tract infection   1/59 (1.69%) 
wound infection   2/59 (3.39%) 
Injury, poisoning and procedural complications   
Wound dehiscence   1/59 (1.69%) 
Musculoskeletal and connective tissue disorders   
muscle weakness left sided   1/59 (1.69%) 
Nervous system disorders   
cerebral spinal fluid leak   2/59 (3.39%) 
headache   1/59 (1.69%) 
stroke   1/59 (1.69%) 
vasovagal reaction   1/59 (1.69%) 
seizure   8/59 (13.56%) 
Psychiatric disorders   
psychiatric disorders - other (steroid induced aggression)   1/59 (1.69%) 
Respiratory, thoracic and mediastinal disorders   
pulmonary edema   1/59 (1.69%) 
Vascular disorders   
hematoma   1/59 (1.69%) 
thromboembolic event   3/59 (5.08%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
5-ALA and Gliadel Wafers
Affected / at Risk (%)
Total   23/59 (38.98%) 
Gastrointestinal disorders   
nausea   4/59 (6.78%) 
vomiting   3/59 (5.08%) 
Injury, poisoning and procedural complications   
wound infection   3/59 (5.08%) 
Investigations   
neutrophil count decreased   4/59 (6.78%) 
platelet count decreased   4/59 (6.78%) 
white blood cell decreased   3/59 (5.08%) 
Musculoskeletal and connective tissue disorders   
muscle weakness   5/59 (8.47%) 
Nervous system disorders   
seizure   5/59 (8.47%) 
lethargy   3/59 (5.08%) 
Vascular disorders   
thrombolytic event   4/59 (6.78%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results.
Results Point of Contact
Name/Title: GALA-5 Trial Coorinator
Organization: University College London
Phone: 0207 679 9898
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01310868     History of Changes
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 Submitted: March 5, 2011
First Posted: March 9, 2011
Results First Submitted: May 2, 2017
Results First Posted: August 14, 2017
Last Update Posted: October 5, 2017