Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma

Study Overview
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Brief Summary
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A study to determine the feasibility and safety of individualized cancer stem cell targeted therapy based on high-throughput functional profiling of FDA/EMA-approved drugs in patients with GBM that has recurred or progressed following standards-of-care (RT, TMZ).

Detailed Description
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This protocol describes a prospective single-center phase 1 study to evaluate the feasibility and safety of a high-throughput drug sensitivity and resistance testing (HTS) platform of individualized cancer stem cells (CSC) to predict targeted therapies in patients with recurrence of GBM after standards-of-care. Secondary outcome include efficacy of drug treatment. The underlying hypotheses is that treatment of patients based on functional profiling og autologous CSCs using HTS a) is feasible within an acceptable time window for clinical translation, b) safely delay disease progression and c) increase survival. There are increasingly published literature that strongly support the importance of a targeting CSC to improve therapy and prevent tumor recurrence in GBM, as an additional strategy to improve the overall prognosis of patients.

Official Title
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Individualized Systems Medicine Strategy for Targeting Cancer Stem Cells in Patients With Recurrent Glioblastoma (ISM-GBM)

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: Personalized drug combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrence of histologically verified glioblastoma Adequate biopsy to generate enough live cells to allow functional screening Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Must be 18 to 70 years of age Adequate bone marrow, liver and heart function Must be competent to give consent Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization Good Clinical Practice guidelines (ICH GCP), and national/local regulations. Exclusion Criteria: Patients taking part in other clinical trials which could make inclusion or follow-up difficult Any reason why, in the opinion of the investigator, the patient should not participate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Open labelled intervention study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients will be treated with drugs based on functional profiling of autologous tumor cells in vitro | Drug: Personalized drug combination<br>* A personalized drug combination will be prescribed to each patient based on the functional drug screen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug screen completion and treatment initiation | The fraction of patient that can receive an individualized treatment based on drug screening. These drugs must be available for treatment and with a combined acceptable toxicity. | 8 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor response by the chosen drug combination evaluated according to the updated response assessment in neuro-oncology (RANO) criteria. | 15 months from inclusion | 
| Number of grade 3-5 adverse events | Adverse events induced by selected treatments according to NCI Common Terminology Criteria for Adverse Events. | 15 months from inclusion | 
| Overall survival | Overall survival in treated patients from time of second surgery to all-cause mortality. | 15 months from inclusion | 
| Patient reported quality of life, overall (QLQ-C30) | Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse. | 15 months from inclusion | 
| Patient reported quality of life, brain specific(QLQ-BN20) | Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse. | 15 months from inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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functional screening, personalized treatment