PTCs-based Precision Treatment Strategy on Recurrent High-grade Gliomas

Study Overview
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Brief Summary
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This trial is an open-label, single-arm, phase 0/1 study of high-grade glioma that aims to evaluate the feasibility, preliminary efficacy and safety of the precision treatment strategy.

Detailed Description
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The investigators have established a precision treatment strategy, that select chemotherapeutic drugs or targeted drugs based on information from PTCs drug-screening or/and bioinformatic prediction. In this study, the investigators are going to exploit this strategy for the precision treatment of recurrent high-grade gliomas. The investigators will evaluate the feasibility, safety and preliminary efficacy via collecting the indexes comprising clinical presentation, results of imaging examination, clinical assays, KPS, neurological score, etc.

Official Title
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Study on Precision Treatment Strategy Through PTCs (Patient-derived Tumor-like Cell Clusters)-Based Drug Screening for Recurrent High-grade Gliomas

Conditions
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Recurrent High Grade Glioma

Intervention / Treatment
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* Drug: Receiving chemotherapeutic or targeted drugs recommended by molecular tumor board.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 At the age of 18 75, regardless the gender 2 The lesion of primary surgery was diagnosed as WHO II IV Glioma by histologic pathology 3 Received radiotherapy and Temozolomide-based chemotherapy within 5 years 4 Recurrent and respectable gliomas, and have been neurosurgically resected 5 The resected recurrent gliomas was identified as WHO III IV Glioma by histologic pathology 6 None postoperative standard therapeutic regimens can be followed when participating the recruitment 7 Can understand the trial's content and sign informed consent Exclusion Criteria: 1 Having other untreated malignant tumors 2 The amount of resected tumors is not enough for genomic sequencing or PTCs drug screening 3 Received Carmustine implants within 6 months prior to enrollment 4 Subjects with active HBC, HCV or HIV infection 5 Subjects with uncontrolled cardio- or cerebro- vascular diseases 6 Subjects with uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes 7 Subjects with other conditions in their active phase that would interfere trial participation 8 Subjects receiving immunosuppressants after organ transplantation 9 Subjects with unstable pulmonary embolism, deep venous embolism, or other major arterial and venous thromboembolic events that occur within 30 days before the enrollment, or receiving anticoagulant therapy 10 Subjects in pregnancy or breastfeeding, or those who plan to become pregnant during treatment or within 2 months after the end of treatment 11 Subjects with other conditions that would interfere participating in the trial at the investigator's discretion 12 Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures; or patients who are unwilling or unable to comply with the research procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Receiving chemotherapeutic or targeted drugs recommended by molecular tumor board.<br>These drugs included all the FDA-approved drugs that have been used in treating gliomas. A single drug or a drug combination for a specific patient will be recommended by the molecular tumor board, comprising neurooncologists, neurosurgeons, pharmacologists, cancer biologists, radiologists and bioinformaticians, will recommend , based on their expertise, patients willingness as well as evidences from PTCs-drug screening and bioinformatic prediction for drug response. | Drug: Receiving chemotherapeutic or targeted drugs recommended by molecular tumor board.<br>* Patients will be treated with FDA-approved chemotherapeutic or targeted drugs which were recommended by the molecular tumor board (MTB), based on their expertise, patients willingness as well as evidences from PTCs-drug screening and bioinformatic prediction for drug response.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients who accomplish the recommended regimen for at least 1 course. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (AEs) | AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | From the first shot to 4 weeks after the last shot | 
| Ratio of 6 months overall survival (OS) | Percentage of patients who survived more than 6 months from the date of surgery to death | 6 months | 
| Ratio of 12months overall survival (OS) | Percentage of patients who survived more than 12 months from the date of surgery to death | 12 months | 
| Progression-free survival (PFS) | Progression-free survival, time from the date of surgery to any types of progression | 24 months | 
| Overall survival (OS) | Overall survival, time from the date of surgery to death for whatever reason | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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precision medicine, organoid-based drug screening, bioinformatic prediction for drug response