Fluorescence and Glioma Heterogeneity

Malignant Gliomas Clinical Trial

— ALAglioma  

Official title:

Understanding the Mechanisms of ALA-induced Fluorescence in Malignant Gliomas - Exploring the Biological Basis of Tumoral Heterogeneity.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02155452
• Other study ID #: TMC- ACTREC IRB project no 139
• Status: Completed
• Start date: May 2014
• Est. completion date: July 2019

Study information

• Verified date: May 2022
• Source: Tata Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by sampling tissues from these variable areas within the same tumor. These tissue samples will then be subjected to pathological and biological analysis to assess proteins related to ALA metabolism and correlated with the fluorescence emitted as well as levels of protoporphyrin IX in the tissues.

Description:

Malignant gliomas are the commonest malignant brain tumors but are extremely challenging to treat. Neuro-oncology has seen little progress in its treatment despite extensive research. Extent of resection remains a very important prognostic factor in these tumors. Better the resection, better the outcomes. However resecting these tumors is not very easy primarily due to their infiltrative nature and difficulty in discerning tumor boundaries intraoperatively. Fluorescence guided resection (FGR) has recently been shown to be a very important and useful adjunct in maximizing this goal. FGR involves administration of aminolevulinic acid (ALA) to the patient prior to surgery. The ALA is converted to protoporphyrin IX (PPIX) in glioma cells. The PPIX is a fluorophore and can be visualized intraoperatively using a suitably modified microscope. Neurosurgeons can then resect the tumor radically guided by this fluorescence which is superior to the conventional microscopic resection. Selective PPIX accumulation in glioma cells is the key to the accuracy of this technique. The biological basis of selectivity of PPIX accumulation within glioma cells is however poorly understood. Various mechanisms could be involved starting from variable transport (related to blood-brain barrier properties), differential uptake (governed by active transport mechanisms) and differential metabolism within the cell. Understanding these mechanisms can lead to refinements in this strategy, overcoming its present limitations and development of methods to extend its scope.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Per-primum glioma

• Adults (18-65 years)

• Radiologically suspected malignant gliomas

• Variable contrast enhancement on MRI (patchy and/or non-uniform)

• Eligible for surgical therapy (craniotomy NOT stereotactic biopsy )

• No contraindication for surgery

Exclusion Criteria:

• Poor general condition (KPS < 70)

• Prior treatment (except biopsy)

• Compromised renal/hepatic function

• Immunocompromised status

• Known photosensitivity / allergy to 5-ALA

Related Conditions & MeSH terms

• Glioma
• Malignant Gliomas

Intervention

Procedure:
• ALA
Prior to surgery all patients would receive freshly prepared solution of 5-ALA, 20 mg/kg bodyweight dissolved in 100 ml of potable water orally approximately 4 hours (range 4-6 hrs) before the commencement of anesthesia induction for surgery. The surgery would then be performed with the help of navigation. After craniotomy, the navigation software would be used to identify the selected target areas based on the preoperative images (MR as well as PET when available) and directed image-guided biopsies from these representative areas will be collected for histological evaluation

Locations

Country	Name	City	State
India	Advanced Centre for Treatment, Research & Education in Cancer (ACTREC)	Navi Mumbai	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Tata Memorial Hospital

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Degree of fluorescence	Degree of fluorescence in different tumor regions; PPIX Qualification	At the time of surgery within 72 hours
Secondary	High throughput proteomic screening of tissue samples	-A quantitative approach will be undertaken to compare the proteome profile	Postoperatively within 1 week of the excision