INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial

Dupont, Clément; Vermandel, Maximilien; Leroy, Henri‐Arthur; Quidet, Mathilde; Lecomte, F.; Delhem, Nadira; Mordon, Serge; Reyns, Nicolas

doi:10.1093/neuros/nyy324

Cited by 83 publications

(68 citation statements)

References 25 publications

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“…In 2017 a clinical trial was initiated to evaluate the use of 5-ALA as a PDT agent (INDYGO, NT number: NCT03048240) where illumination of 5-ALA-stained tissue is added to the conventional standard of care protocol. The results have not yet been posted and evidence for added value of this approach is currently still lacking [55]. Another trial with 5-ALA, which is currently registered at ClinicalTrials.gov (NCT03897491) by Photonamic GmbH&Co.KG, "PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma", is not yet recruiting.…”

Section: Pdt Of Gbm With Porphyrinsmentioning

confidence: 99%

Using Light for Therapy of Glioblastoma Multiforme (GBM)

et al. 2020

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Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentially inevitable. The key reason for that is that the surgical treatment fails to eradicate GBM cells completely, and adjacent parenchyma remains infiltrated by scattered GBM cells which become the source of recurrence. This stimulates interest to any supplementary methods which could help to destroy residual GBM cells and fight the infiltration. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells or, perhaps their greater sensitivity to the effects, triggered by light. This gives hope that it might be possible to preferentially damage infiltrating GBM cells within the areas which cannot be surgically removed and further improve the chances of survival if an efficient photosensitiser and hardware for light delivery into the brain tissue are developed. So far, clinical trials with PDT were performed with one specific type of photosensitiser, protoporphyrin IX, which tends to accumulate in the cytoplasm of the GBM cells. In this review we discuss the idea that other types of molecules which build up in mitochondria could be explored as photosensitisers and used for PDT of these aggressive brain tumours.

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Section: Pdt Of Gbm With Porphyrinsmentioning

confidence: 99%

Using Light for Therapy of Glioblastoma Multiforme (GBM)

et al. 2020

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“…Thus, the degree of oxygenation with the tumor microenvironment is a key determinant of PDT's tumoricidal activity. In this context, PDT is often delivered through multi-session treatment in order to facilitate re-oxygenation between treatments (16,17). Preclinical and clinical trials of PDT performed in combination with hyperbaric oxygen demonstrate improved tumoricidal activity (18).…”

Section: Principle Of Photodynamic Therapy (Pdt)mentioning

confidence: 99%

“…All photostimulation fractions are delivered in the operating room. This is the approach being utilized in the Intraoperative Photodynamic Therapy of glioblastoma (INDYGO) clinical trial which is currently ongoing (17).…”

Section: Post-resection Pdtmentioning

confidence: 99%

Photodynamic Therapy for the Treatment of Glioblastoma

2020

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Glioblastoma is the most common form of adult brain cancer and remains one of the deadliest of human cancers. The current standard-of-care involves maximal tumor resection followed by treatment with concurrent radiation therapy and the chemotherapy temozolomide. Recurrence after this therapy is nearly universal within 2 years of diagnosis. Notably, >80% of recurrence is found in the region adjacent to the resection cavity. The need for improved local control in this region, thus remains unmet. The FDA approval of 5-aminolevulinic acid (5-ALA) for fluorescence guided glioblastoma resection renewed interests in leveraging this agent as a means to administer photodynamic therapy (PDT). Here we review the general principles of PDT as well as the available literature on PDT as a glioblastoma therapeutic platform.

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“…5-ALA use in glioma surgery was reviewed twice in 2017 [15,29]. Four papers published in 2018 recounted the various factors active in determining degree of GB cells' PpIX content [2][3][4][5]. Since 100% of strongly fluorescing tissue during 5-ALA assisted surgery was clearly GB tissue but 49% of non-overtly fluorescing resection margin tissue also contained a few GB cells or cell islands, if we can indeed increase 5-ALA uptake and conversion to PpIX as aimed for with CAALA, we might be able to catch microfoci of GB tissue in PDT that would be otherwise missed [30]: The fundamental idea behind CAALA.…”

Section: Intraoperative Fluorescence Tumor Demarcationmentioning

confidence: 99%

“…PpIX emits a photon that results in cytotoxicity after exposure to ~ 410 nm or ~ 635 nm light. Both uses rest on the relatively selective uptake into GB cells and intracellular conversion to PpIX, commonly found to be 50:1 compared to non-malignant glia [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen

Kast¹,

Skuli

Sardi³

et al. 2018

Preprint

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The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its selective conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently marketed drugs - the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat - that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

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INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial

Cited by 83 publications

References 25 publications

Using Light for Therapy of Glioblastoma Multiforme (GBM)

Using Light for Therapy of Glioblastoma Multiforme (GBM)

Photodynamic Therapy for the Treatment of Glioblastoma

Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen

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