Clinical trial NCT03180697: The Efficacy of APT Magnetic Resonance Imaging in Predicting the Efficacy of Bevacizumab in Recurrent Malignant Gliomas
Official title: Clinical Study on the Efficacy of Amide Proton Transfer Magnetic Resonance Imaging in Predicting the Efficacy of Bevacizumab in Recurrent Malignant Gliomas
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diagnoses Disease
Glioma of Brain
Keywords: Amide Proton Transfer
bevacizumab
recurrent malignant gliomas
efficacy
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: Nanfang Hospital, Southern Medical University
First posted: 2017-06-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 100 patients with recurrent maligant glioma will be recuritted. All the patients are eligible for the inclusive criteria.

Brief summary: Targeted therapy with bevacizumab is the main method to prolong the progression-free survival of patients with recurrent malignant gliomas in recent years. Using noninvasive imaging methods to predict which RMG may respond to bevacizumab regimen therapy is a clinical problem ; on the other hand, repeated gadolinium enhancement may increase the risk of gadolinium ion deposition of brain tissue. Furthermore,there may be a false response phenomenon and cause assessment bias.in the evaluation of treatment efficacy,owing to bevacizumab is only anti-tumor angiogenesis.

Amide Proton Transfer (APT) is a new molecular imaging technique. Our previous studies have shown that imaging features and signal changes of APT can fully reflect the therapeutic effect of malignant glioma,without the injection of contrast agent and avoid the side effects.

RMG patients will be recruited in this study . This project will be designed multi-center, prospective, observational clinical research. The changes of APT signal intensity before and after treatment will be compared with those of different types of RMG line. The relationship between APT imaging characteristics and clinical end point events will be investigated and compared with conventional MR imaging technique. The sensitivity, specificity and accuracy of the progression-free survival and median overall survival will be measured after treatment with bevacizumab.

Detailed description: Recurrent Malignant Gliomas (RMG) have a very short survival time, and re-operation risk is large and failed to significantly improve the prognosis of patients. At present, targeted therapy with bevacizumab is effective in prolonging the progression of patients However, a considerable proportion of recurrent malignant gliomas are insensitive to bevacizumab, and therefore, using noninvasive imaging methods to predict which RMG is sensitive to bevacizumab therapy prior to targeted therapy is very important On the other hand, the current evaluation of bevacizumab is mainly based on the degree of gadolinium enhancement and tumor volume changes, repeated gadolinium injection may increase the risk of gadolinium ion deposition of brain tissue, and because of Bevacizumab only acting as an anti-tumor angiogenesis, and a false response may occur in assessing efficacy, which is a bias in the overall assessment of bevacizumab.

Amide Proton Transfer (APT) is a new molecular imaging technique for the detection indirect of free protein and peptide concentrations based on chemical saturation exchange. Our previous studies have shown that APT signal is independent of gadolinium-enhanced imaging markers , The signal intensity is closely related to the density of tumor cells, cell proliferation and angiogenesis. Therefore, the imaging features and signal changes of APT can fully reflect the therapeutic effect of malignant glioma, and avoid the side effects caused by contrast injection.

This study will be designed as multi-center, prospective, observational clinical research. 100 cases of RMG patients in Zhujiang Hospital and Nanfang Hospital will be recruited. The patients will be examined with conventional MRI and APT-MRI imaging of 3.0T high field MRI. The treatment of different types of RMG line will be scanned with APT protocol. The changes of signal intensity will be studied. The relationship between APT imaging characteristics and clinical end point events will be observed and compared with conventional MR imaging technique. Two techniques will be used to predict the the 6-month progression-free survival after bevacizumab treatment. The aim of this study is to determine whether APT can predict the efficacy of bevacizumab in the treatment of RMG, and which RMG is effective and sensitive to bevacizumab therapy .Also,we will evaluate the feasibility of APT-MR imaging as a surrogate biomarker for predicting the efficacy of targeted therapy and to establish the basic criteria for the selection of individualized targeted therapy regimens for RMG.

Eligibility criteria: Inclusion Criteria:

1. malignant glioma patients at least 4 weeks after surgery;
2. after radiotherapy or chemotherapy after the recurrence, stop to put,
3. the age of patients ≥ 18 years old;
4. bone marrow, liver and kidney function is good;
5. not using steroid hormones or disabled for more than 5 days;
6. patients are generally in good condition, expected survival is greater than 8 weeks, Karnofsky test is greater than 60.

Exclusion Criteria:

1. patients with refractory hypertension, active vascular disease, bleeding, intestinal perforation and other medical history;
2. frail and difficult to tolerate treatment;
3. HIV positive;
4. pregnant or lactating.

Primary outcomes:
measure: Signal intensity of tumor on APT imaging
timeFrame: From date of confirmed recurrence until the date of deterioration or date of death from any cause. That means measure, assessed APT signal intensity at 6 weeks, 12 weeks,18 weeks and so on, assessed up to 1 year.
Secondary outcomes:
measure: Dimension of tumor on Gd-enhanced MRI
timeFrame: Measure tumor dimension at 6 weeks, 12 weeks and 18 weeks for the most. It will be ended at any time the patient dies.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
Study officials:
affiliation: Institutional Ethics Review Board
name: Xiaoxiao Wu, Master
role: PRINCIPAL_INVESTIGATOR
References: