Accelerated Hypofractionated Intensity - Modulated Radiotherapy After Hyperbaric Oxygenation for Recurrent High Grade Glioma.

Study Overview
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Brief Summary
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This is a pilot study of radiotherapy using Hypofractionated image - guided helical tomotherapy after hyperbaric oxygen HBO therapy for treatment of recurrent malignant High-grade gliomas. HBO therapy will be perform in conjunction with each RT session. The treatment scheme is: Hyperbaric oxygenation therapy (the maximum period of time from completion of decompression to RT is 60 min) followed by tomotherapy (3-5 consecutive sessions- one fraction per day , 5 Gy / die ). The trial will enroll 24 patients in 24 months with a follow-up period of 1 year.

Detailed Description
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This is a pilot study to evaluate the efficacy of hypofractionated image- guided helical tomotherapy after hyperbaric oxygen therapy (HBO) for treatment of recurrent malignant high - grade gliomas The primary objective of this study is to evaluate the disease control rate (DCR) of treated patients. The secondary Objectives are: Safety assessment (acute and late toxicity). Overall Survival (OS), Progression Free Survival (PFS). Evaluation of predictive score of disease, radionecrosis and pseudoprogression using perfusion DSC and DCE MRI Patients will receive fractionated stereotactic radiotherapy using tomotherapy combined with hyperbaric oxygen (HBO) therapy. Hyperbaric oxygenation therapy (the maximum period of time from completion of decompression to RT is 60 min) followed by tomotherapy (3-5 consecutive sessions- one fraction per day, 5 Gy / die). The overall duration of treatment will be max 5 days.

Official Title
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Accelerated Hypofractionated Intensity - Modulated Radiotherapy After Hyperbaric Oxygenation for Recurrent High Grade Glioma: a Pilot Study

Conditions
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Malignant Glioma, High Grade Glioma, Recurrent Glioma

Intervention / Treatment
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* Device: HBO
* Radiation: RT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, aged >18 years. Karnofsky Performance Scale (KPS)> 60 Imaging confirmation of first tumor progression o regrowth as defined by Response Assessment in Neuro-Oncology Criteria (RANO) criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented Recurrence after adjuvant treatment( surgery followed by radiotherapy and chemotherapy) in patients who could receive further therapeutic interventions No more than one prior line of chemotherapy (one line of chemotherapy after concurrent and adjuvant Temozolomide (TMZ) - based chemotherapy or procarbazine/lomustine/vincristine (PCV) - Radiotherapy (RT) Patients who have undergone recent surgery for recurrent o progressive high grade gliomas are eligible provided that : surgery must have confirmed the recurrence ; a minimum of 28 days must have elapsed from the days of surgery to study . For core or needle biopsy a minimum of 7 days must have elapsed prior to study . If female and of child bearing potential , have a negative result on a pregnancy test performed a maximum of 7 days before initiation . Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 4 months thereafter Have adequate bone marrow function , liver function , and renal function , as measured by following laboratory assessments conducted within 7 days prior to the initiation of study treatment . Hemoglobin >9.0 g/dl Absolute neutrophil count (ANC) >1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors Platelet count ≥90,000/μl White Blood Cell (WBC) >3.0 x 109/L Total bilirubin <1.5 times the upper limit of normal Serum creatinine <1.5 x upper limit of normal Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: Radiotherapy within 12 weeks prior to the diagnosis of progression, if the lesion is in the radiation field. Patients with cardiopulmonary diseases (heart failure, bolus emphysema, pneumothorax, chronic obstructive pulmonary disease (COPD) with hypercapnia sinusitis ) Closed angle-glaucoma with pressure ocular superior to 24 mmHg

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBO and RT<br>Hyperbaric oxygenation therapy and Accelerated Hypofractionated intensity - modulated radiotherapy | Device: HBO<br>* Hyperbaric oxygen is administrated in a multiplace hyperbaric chamber according to the following schedule: Ten minutes of compression with a Fraction of inspired oxygen (FiO2) more than 90% from 152 to 253 kilopascal, 60 minutes of Fraction of inspired oxygen (FiO2) more than 90% at 253 kilopascal (three breathing cycles in oxygen for 22 minutes each, with two intervals breathing air for 2 minutes each) and 10 minutes of decompression with a Fraction of inspired oxygen (FiO2) more than 90% from 253 to 152 kilopascal.<br>Radiation: RT<br>* tomotherapy (within 60 minutes from completion of decompression of hyperbaric chamber) with 3-5 consecutive sessions- one fraction per day, 5 Gy / die .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | DCR will be evaluated by performing MRI images The treatment response will be evaluated according to the RANO criteria | up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria Events v. 4.03. | up to 36 months | 
| Overall survival (OS) | OS will be defined as the time from the first day of treatment to death due any cause or censored at date last known alive | up to 36 months | 
| Progression Free survival (PFS) | PFS will be calculated as the time from the first day of treatment to the date of the first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation. | up to 36 months | 
| Predictive score of disease progression by DSC MRI | determining a predictive score of disease, using perfusion dynamic contrast-enhanced (DSC) permeability MRI | up to 36 months | 
| Radionecrosis by DSC MRI | determining radionecrosis using perfusion dynamic contrast-enhanced (DSC) permeability MRI | up to 36 months | 
| Pseudoprogression by DSC MRI | determining pseudoprogression using perfusion dynamic contrast-enhanced (DSC) permeability MRI | up to 36 months | 
| Predictive score of disease progression by DCE MRI | determining a predictive score of disease using dynamic susceptibility contrast (DCE) perfusion MRI | up to 36 months | 
| Radionecrosis by DCE MRI | determining radionecrosis using dynamic susceptibility contrast (DCE) perfusion MRI | up to 36 months | 
| pseudoprogression by DCE MRI | determining pseudoprogression using dynamic susceptibility contrast (DCE) perfusion MRI | up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated radiotherapy, image - guided helical tomotherapy, hyperbaric oxygen therapy, malignant glioma, high grade glioma, recurrent glioma