Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma

Study Overview
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Brief Summary
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The phase II study evaluate a light dose escalation in a classical intraoperative PDT regimen mediated by 5-ALA-PpIX, in glioblastoma patients with access to full surgical removal of the contrast enhancement. This treatment will be performed in addition to the current reference treatment of glioblastoma: maximum removal surgery followed by radiochemotherapy according to the Stupp protocol.

Official Title
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A Multi-center Phase II Study With Light Dose Escalation During Intraoperative Photodynamic Therapy of Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Gliolan
* Device: Intraoperative PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General status (WHO) Karnofsky Performance Status ≥60 Presumptive glioblastoma according to radiological criteria, Surgical indication decided in Multidisciplinary consultation meeting (RCP) of neuro oncology, Decision to treat the patient as part of the Clinical trial achieved in neuro-oncology RCP (Multidisciplinary consultation meeting) Patient operable on the basis of absence of cardiopulmonary disease history; a complete medical check-up sufficient to insure a post-operative state with normal daily life Clinical neuro-oncological monitoring and long-term MRI/ TEP 11C MET scheduled at the hospital centers Patient able to understand and sign voluntarily Informed consent Patient able to adhere to the visit's calendar of the study and other imperatives of the protocol Women of child-bearing potential should benefit of an effective contraception For patients receiving hepatotoxic therapy in the long term, this treatment must be suspended during the 24h after taking 5-ALA Exclusion Criteria: Contraindications to 5-ALA (Gliolan®) and to intra-operative PhotoDynamic Therapy intraoperative PDT: Contraindications to 5-ALA Porphyria Taking photosensitizer treatment Severe renal or hepatic impairment Bilirubin> 1.5 x maximum level, Alkaline Phosphatases and transaminases (ASAT)> 2.5 x Maximum. rates Creatinine clearance <30 mL / min; Non-compliance with the rules of prevention of the transient risk of cutaneous photosensitization Contraindications to surgery Contraindications to magnetic resonance imaging (MRI/TEP 11C MET Treatment with an experimental drug within 30 Days prior to the start of the study Clinical follow-up impossible to perform for psychological, familial, social or geographical reasons, Legal incapacity (persons deprived of their liberty or Guardianship or guardianship), Pregnant or nursing women Refusal to participate or sign the consent of the study Soy allergy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intraoperative PDT 400J/cm²<br> | Drug: Gliolan<br>* patient will receive 5-ALA 4 to 6 hours before surgery<br>Device: Intraoperative PDT<br>* The protocol requires the realization of specific procedures in addition to the usual care. The intra-operative photodynamic therapy (intraoperative PDT) added to surgery for glioblastoma excision. The patient will receive 5-ALA ( 5-aminolevulinic acid hydrochloride),GLIOLAN drinkable 6h before surgery + lighting of the tumor bed by a red light source (laser with different J/cm²) at the end of resection (Prolonged surgery of 45 minutes).<br>|
| Experimental: intraoperative PDT 600J/cm²<br> | Drug: Gliolan<br>* patient will receive 5-ALA 4 to 6 hours before surgery<br>Device: Intraoperative PDT<br>* The protocol requires the realization of specific procedures in addition to the usual care. The intra-operative photodynamic therapy (intraoperative PDT) added to surgery for glioblastoma excision. The patient will receive 5-ALA ( 5-aminolevulinic acid hydrochloride),GLIOLAN drinkable 6h before surgery + lighting of the tumor bed by a red light source (laser with different J/cm²) at the end of resection (Prolonged surgery of 45 minutes).<br>|
| Experimental: intraoperative PDT 800J/cm²<br> | Drug: Gliolan<br>* patient will receive 5-ALA 4 to 6 hours before surgery<br>Device: Intraoperative PDT<br>* The protocol requires the realization of specific procedures in addition to the usual care. The intra-operative photodynamic therapy (intraoperative PDT) added to surgery for glioblastoma excision. The patient will receive 5-ALA ( 5-aminolevulinic acid hydrochloride),GLIOLAN drinkable 6h before surgery + lighting of the tumor bed by a red light source (laser with different J/cm²) at the end of resection (Prolonged surgery of 45 minutes).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose-Light Level (MTDL) defined as the light dose associated with an acceptable dose-limiting toxicity level (TDL) | Dose level above which TDL is observed in more than 33% (i.e., d̀-> 2 of 6) of subjects in an arm | 4 weeks (+/-3 days) post-PDT. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Number of patients without relapse within 25 mm of surgical site defined according to International RANO criteria | From the Date of diagnosis of glioblastoma until the date of Relapse, an average 18 months | 
| Global Progression Free Survival (PFS) | Median of progression-free survival time determined according to international RANO criteria | From the Date of diagnosis of glioblastoma until the date of Relapse, an average 18 months | 
| Overall Survival (OS) | Median of OS determined according to international RANO criteria | From the Date of diagnosis of glioblastoma until the death, an average 18 months | 
| Response to treatment | Evaluated by MRI/ TEP 11C-MET every 3 months | every 3 months between the Date of intraoperative PDT until relapse/death, an average 18 months | 
| Incidence of intraoperative PDT treatment-emergent Adverse Events | Collection of all Adverse events (AEs and SAEs) (according to NCI-CTCE V5.0) and reviewing by an Independent Safety Monitoring Board | From the beginning of treatment with intraoperative PDT up to relapsing/death, an average 18 months | 
| Quality of Life Questionnaire -C30 ( QLQ-C30 | The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items | Every 3 months from the signature of Consent form until relapse/death, an average 18 months | 
| Quality of Life Questionnaire - Brain Cancer Module (QLQ-BN20) | Measuring the health-related quality of life in patients with brain cancer | Every 3 months from the signature of Consent form until relapse/death, an average 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Photodynamic Therapy, Neurosurgery, Oncology, 5-aminolevulinic Acid, Surgical indication of glioblastoma, Glioblastoma