Clinical trial NCT02155452: Fluorescence and Glioma Heterogeneity
Official title: Understanding the Mechanisms of ALA-induced Fluorescence in Malignant Gliomas - Exploring the Biological Basis of Tumoral Heterogeneity.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malignant Gliomas
Keywords: ALA
Malignant gliomas
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
First posted: 2014-06-04
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with malignant glioma

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Degree of fluorescence
timeFrame: At the time of surgery within 72 hours
Secondary outcomes:
measure: High throughput proteomic screening of tissue samples
timeFrame: Postoperatively within 1 week of the excision
Other outcomes:
Locations:
city: Navi Mumbai
country: India
facility: Advanced Centre for Treatment, Research & Education in Cancer (ACTREC)
state: Maharashtra
Study officials:
affiliation: neurosurgeon
name: Aliasgar V Moiyadi, MCh DNB
role: PRINCIPAL_INVESTIGATOR
References: