Imaging and Biological Markers for Prediction and Identification of Glioblastoma Pseudoprogression: a Prospective Study.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 75
- Locations
- 2
- Primary Endpoint
- Predictive models of pseudoprogression
Study Overview
Brief Summary
The goal of this interventional study is the development and validation of imaging markers, MRI and PET, plasma biomarkers, and/or cell markers that could support clinicians and researchers in differentiating pseudoprogression from true tumor progression in routine clinical activities and clinical trials in patients affected by glioblastoma.
The endpoints of the study are:
- the elaboration of predictive models using imaging advanced biomarkers, PET and MRI, biological serum markers, and cancer cell derived makers to differentiate tumor pseudoprogression or real progression in patients affected by glioblastoma who underwent therapeutical protocol as per treating physicians' indications (Stupp or hypofractionated RT)
- to establish an in vivo murine model of pseudoprogression by orthotopic transplantation of glioblastoma stem cells derived from thirty-five patient subjected to subsequent treatment with irradiation and temozolomide administration.
Participants will undergo:
- baseline MRI and 18F-GE-180 PET imaging, and blood withdrawal
- surgery
- collection of glioblastoma stem cells (and hematopoietic stem cells from a sub-group of subjects)
- standard treatment with radiotherapy and chemotherapy
- MRI every 3 months
- PET and blood withdrawal in case of MRI evidence of either suspected tumor progression or pseudoprogression
- second surgery OR stereotactic biopsy OR clinico-radiological follow-up as for standard of care according to the Institutional Multidisciplinary Brain Tumor Board
Detailed Description
Rationale
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system characterized by an extremely severe prognosis with a median survival of 14-16 months from diagnosis. Patients affected by high-grade gliomas are treated with a combination of radiotherapy and temozolomide chemotherapy. To date, the efficacy of the treatment is assessed through MRI which shows evidence of early radiological progression in up to 50% of all patients. Importantly, signs of tumor progression on MRI images may actually represent pseudoprogression in up to 64% of cases meaning that within 6 months from the end of the radiation treatment 20-30% of patients show increased contrast enhancement that resolves on subsequent MRI scans without changes in the treatment. Pseudoprogression is a phenomenon likely related to inflammation and disruption of the blood-brain barrier (BBB) caused by radiation and by the concurrent temozolomide treatment. Being a self-resolving consequence of the therapy rather than a sign of tumor growth, mistaking pseudoprogression for real progression leads to premature discontinuation of therapy and inappropriate evaluation of progression free survival and response rate in clinical trials impairing clinical practice.
Therefore, the differentiation of pseudoprogression from true progression is both a challenge in everyday clinical activity and a relevant problem in clinical trials and research.
A major limitation to the development and assessment of efficacy of current and new therapies in the setting of brain tumors, both at preclinical and clinical levels, however, is the lack of reliable trial endpoints.
A combination of advanced imaging methods, MRI and PET, with innovative techniques investigating cancer-specific biology will allow a holistic characterization of the tumor from multiple aspects crucial to enable a personalized diagnostic and therapeutical approach.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients of both sex and any race age >=
- •Histologically proven glioblastoma multiforme wild type for IDH1-2 mutation with MGMT promoter methylated or unmethylated OR subjects with medical history, clinical sign and symptoms and MRI findings highly consistent with the diagnosis of IDH wild type glioblastoma.
- •Patient eligible to undergo treatment with TMZ and RT (Stupp protocol or hypofractionated protocol as per Institutional Multidisciplinary Brain Tumor Board's decision)
- •Willingness and ability to sign the informed consent and participate to the trial.
Exclusion Criteria
- •Patient age <
- •Patient not eligible to undergo treatment with TMZ and RT (Stupp protocol or hypofractionated protocol as per Institutional Multidisciplinary Brain Tumor Board's decision).
- •Patient presenting contraindication to undergo contrast-enhanced MRI (pacemaker or allergy to gadolinium).
- •Patient HIV1-2 positive.
- •Patient affected by other systemic infective or inflammatory diseases or involving the central nervous system (multiple sclerosis, lupus, Chron, rheumatoid arthritis).
- •Patients that are pregnant or breast-feeding. -
Outcomes
Primary Outcomes
Predictive models of pseudoprogression
Time Frame: From baseline assessment to the last visit of the patient as per protocol
predictive models (evaluation of specificity and sensitivity) using imaging advanced biomarkers, PET and MRI, biological serum markers, and cancer cell derived makers to differentiate tumor pseudoprogression or real progression in patients affected by GBM who underwent therapeutical protocol as per treating physicians' indications (Stupp or hypofractionated RT)
Secondary Outcomes
- Glioblastoma Stem Cells (GSCs) isolation and in vitro model(starting from the day of the first surgery)
Investigators
Michele Tedeschi
Research Administrator Manager
Istituto Clinico Humanitas