Trial Outcomes & Findings for Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma (NCT NCT01310868)

Last Updated: 2017-10-05

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)

Results posted on

2017-10-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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: 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 Study STARTED	72
Overall Study COMPLETED	59
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	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: 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 Study Do not have histologically confirmed GBM	13

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5-ALA and Gliadel Wafers n=72 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	54 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants
Region of Enrollment United Kingdom	72 participants n=5 Participants

PRIMARY outcome

Timeframe: Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks)

Population: 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

Outcome measures

Outcome measures
Measure	5-ALA and Gliadel Wafers n=72 Participants 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.
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide 5-ALA resected patients receiving carmustine wafer	62 Participants
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide No. patients with post-op complications	9 Participants
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide No. Patients with chemoRT delay	6 Participants
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide No. pts failing to complete uninterrupted chemoRT	45 Participants
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide no. pts w decr perform status after 5ala/carmustin	27 Participants
Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide no. pts not starting chemoRT due to surgical comp	2 Participants

SECONDARY outcome

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

Population: Patients receiving 5-ala and carmustine wafers during surgical resection for glioblastoma multiforme that was confirmed peri/post-operatively

Outcome measures

Outcome measures
Measure	5-ALA and Gliadel Wafers n=59 Participants 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.
Time to Clinical Progression	9.5 months Interval 7.5 to 9.8

SECONDARY outcome

Timeframe: from the date of surgery to 24 months

Population: Patients receiving 5-ala and carmustine wafers during surgical resection for glioblastoma multiforme that was confirmed peri/post-operatively

Outcome measures

Outcome measures
Measure	5-ALA and Gliadel Wafers n=59 Participants 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.
Survival at 24 Months	15 months Interval 11.9 to 17.3

Adverse Events

5-ALA and Gliadel Wafers

Serious events: 26 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	5-ALA and Gliadel Wafers n=59 participants at risk 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.
Injury, poisoning and procedural complications Wound dehiscence	1.7% 1/59
Vascular disorders hematoma	1.7% 1/59
Vascular disorders thromboembolic event	5.1% 3/59
Respiratory, thoracic and mediastinal disorders pulmonary edema	1.7% 1/59
Nervous system disorders cerebral spinal fluid leak	3.4% 2/59
Nervous system disorders headache	1.7% 1/59
Nervous system disorders stroke	1.7% 1/59
Nervous system disorders vasovagal reaction	1.7% 1/59
Eye disorders retinal detachment	1.7% 1/59
General disorders fever	1.7% 1/59
Psychiatric disorders psychiatric disorders - other (steroid induced aggression)	1.7% 1/59
Gastrointestinal disorders colonic perforation	1.7% 1/59
Gastrointestinal disorders other - bowel perforation	1.7% 1/59
Gastrointestinal disorders intra-abdomial hemorrhage	1.7% 1/59
Gastrointestinal disorders nausea	1.7% 1/59
Gastrointestinal disorders vomiting	1.7% 1/59
Musculoskeletal and connective tissue disorders muscle weakness left sided	1.7% 1/59
Infections and infestations infection - cerebral abscess	1.7% 1/59
Infections and infestations infections other (not specified)	3.4% 2/59
Infections and infestations sepsis	3.4% 2/59
Infections and infestations urinary tract infection	1.7% 1/59
Infections and infestations wound infection	3.4% 2/59
Nervous system disorders seizure	13.6% 8/59

Other adverse events

Other adverse events
Measure	5-ALA and Gliadel Wafers n=59 participants at risk 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.
Injury, poisoning and procedural complications wound infection	5.1% 3/59
Vascular disorders thrombolytic event	6.8% 4/59
Investigations neutrophil count decreased	6.8% 4/59
Investigations platelet count decreased	6.8% 4/59
Investigations white blood cell decreased	5.1% 3/59
Nervous system disorders seizure	8.5% 5/59
Nervous system disorders lethargy	5.1% 3/59
Gastrointestinal disorders nausea	6.8% 4/59
Gastrointestinal disorders vomiting	5.1% 3/59
Musculoskeletal and connective tissue disorders muscle weakness	8.5% 5/59

Additional Information

GALA-5 Trial Coorinator

University College London

Phone: 0207 679 9898

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER