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

NCT01310868 | Completed Phase 2 Results DMC

• 5 other identifiers: CDR0000696316CRUK-UCL-09-03982010-022496-6609/039810/H0304/100
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 10

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.

Conditions

Glioblastoma

Keywords

adult giant cell glioblastoma; adult gliosarcoma; adult glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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)

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

Secondary Outcomes (2)

• Time to Clinical Progression

  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

  from the date of surgery to 24 months

Study Arms (1)

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.

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

Interventions

5-ALA DRUG

5-ALA is used to generate tumour specific fluorescence as an aid to surgical resection of GBM, prior to the insertion of Gliadel wafers

Also known as: Amino-levulinic Acid, Gliolan

5-ALA and Gliadel wafers

Gliadel wafers DRUG

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.

Also known as: Carmustine wafers, polifeprosan 20 with carmustine implant

5-ALA and Gliadel wafers

Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist RADIATION

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

5-ALA and Gliadel wafers

Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist DRUG

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

5-ALA and Gliadel wafers

Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist DRUG

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

5-ALA and Gliadel wafers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead

Study Sites (10)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Southern General Hospital

Glasgow, United Kingdom

Location

Hull Royal Infirmary

Hull, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

The Walton Centre

Liverpool, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

University College London Hospital/ National Hospital for Neurology and Neurosurgery

London, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Aminolevulinic Acid; Carmustine; Radiotherapy; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Therapeutics; Combined Modality Therapy; Drug Therapy

Results Point of Contact

• Title: GALA-5 Trial Coorinator
• Organization: University College London

ctc.sponsor@ucl.ac.uk

0207 679 9898

Study Officials

• Colin Watts

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2011
• First Posted: March 9, 2011
• Study Start: May 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 5, 2017
• Results First Posted: August 14, 2017

Record last verified: 2017-09

Locations

GB (10)