Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Brain Neoplasms

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

bevacizumab 10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (cycle defined as 28 days). If the tumor volume remains \< 40 cc, the patient will undergo stereotactic radiotherapy with IMRT (30Gy) beginning anywhere from day 7-10 of cycle 2 (5 doses of 6 Gy over 2 and a half weeks)

bevacizumab and radiation (IMRT)

Philip Gutin, MD

This is a pilot study. The goal of this study is to test whether Bevacizumab is safe enough in patients with brain tumors so that a larger study can be conducted. This study will also give us some information about whether the combination of Bevacizumab and radiation has potential to become an effective treatment for regrowing brain tumors.

Bevacizumab is an experimental drug that blocks a molecule called VEGF that is found in high amounts in malignant gliomas. VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. In studies with laboratory animals, Bevacizumab slowed the growth of several different types of human cancer cells by blocking the effects of VEGF. There is also evidence that Bevacizumab enhances the effects of radiation on tumor cell

Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma

Safety of Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma: A Pilot Study

Weill Medical College of Cornell University

Genentech, Inc.

Memorial Sloan Kettering Cancer Center

Infections

Adenoviridae Infections

Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.

DNX-2401

Tumor Removal

Frederick F. Lang, MD, BS

The goal of this clinical research study is to find the highest tolerable dose of DNX-2401 that can be injected directly into brain tumors and into the surrounding brain tissue where tumor cells can multiply. A second goal is to study how the new drug DNX-2401 affects brain tumor cells and the body in general.

The Study Drug:

DNX-2401 (formerly known as Delta-24-RGD-4C) is a virus that works by killing brain tumor cells. It is made from a common cold virus, called adenovirus, type 5. This virus normally causes the common cold, and most people around the world have been exposed many times to this common, naturally-occurring virus during their lives. Two (2) changes have been made to the adenovirus to make DNX-2401. The first change was to make the virus only grow in cancer cells. The second change was made to allow DNX-2401 to enter cancer cells more easily. These changes make DNX-2401 more able to multiply and kill cancer cells and less likely to multiply in normal cells.

Study Groups:

Participants will eventually be divided into 2 groups (Groups A and B).

At first, all participants will only be enrolled into Group A. Participants in Group A will receive the study drug but will not have the recurrent malignant glioma tumor removed by surgery.

Enrollment into Group B will not start until the FDA has reviewed initial results on how the treatment for participants in Group A effected brain tumor cells and the body in general. Once approval for enrollment is given, all eligible participants will be assigned to Group B and will receive the study drug and have their tumors removed by surgery. If you are to receive surgery, you will be asked to sign a separate surgical consent form to help further explain the operation.

If you are found to be eligible to take part in this study, you will be assigned to a dose level of DNX-2401 based on when you joined this study. Up 8 dose levels of DNX-2401 will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of DNX-2401 is found. You will be informed of which dose you will receive.

Study Drug Administration:

DNX-2401 is given by a surgical procedure where a neurosurgeon precisely injects DNX-2401 through a catheter (small tube) that is inserted into your brain tumor. You will stay in the hospital and be watched closely afterward for up to 48 hours, but it may be longer if your doctors feel that you are not ready to go home.

After receiving DNX-2401, all participants must wear a mask. You must also stay away from pregnant women, babies, children under three years of age, elderly people and large groups of people who may have weaker defenses to disease or those who can spread a disease. You must also stay away from other patients who may have immune system problems, such as people with AIDS, or people who are getting chemotherapy or radiation therapy. The study doctors will decide how long you will need to follow these precautions. You should not donate blood or sperm for at least 6 months after receiving DNX-2401.

Group A:

Before receiving DNX-2401, participants in Group A will have a sample (stereotactic biopsy) of brain tumor tissue collected to confirm that recurrent malignant glioma is present. On the morning of the biopsy, you will have an MRI (with dye). A metal frame will be placed on your head and an MRI of your brain will be done. Before the MRI, a dye will be injected to help give the doctors a better picture of your brain. The head frame allows the surgeon to use MRI to identify the precise location of the tumor within the brain. The frame will stay in place for several hours while the procedure is being performed.

A portion of your head will be shaved for the biopsy. You will have a small incision (cut) in your head (about 2-3 inches). The protective covering of the brain (dura) will be opened and a piece of brain tumor will be removed. If, under a microscope, the biopsy shows that the tumor is still malignant glioma, you will then have an injection of DNX-2401. The anesthesiologists (doctor who gives the anesthesia) may give you medication to make you sedated (anesthesia). They will place a needle into your vein (intravenous line or "IV") to give you this medicine. The anesthesia is given so that you do not feel any pain or discomfort and do not move during the MRI or the surgery.

A small catheter will be placed into the tumor and the metal frame will help guide the proper placement. Some anti-inflammatory medication (a steroid called dexamethasone) will be given in your vein. Then DNX-2401 will be slowly injected into the tumor over about 10 minutes. After the injection, the incision will be closed in a standard and cosmetically acceptable manner.

Group B:

Before receiving DNX-2401, participants in Group B will have a biopsy to confirm that the tumor is recurrent glioma. The procedure will be exactly the same as described for those in Group A. This is called "Stage 1." However, at the end of the biopsy and study drug injection procedure, the catheter will be clipped off next to your skull and a portion of the tube will remain inside the tumor and in place for the next 2 weeks. The scalp will be closed over the clipped catheter to prevent any possibility of infection. The next day, you will have a CT scan to check the tumor and placement of the catheter.

Group A Follow-up Visits:

You will come back to the study center for check-ups at 4, 7,14 and 28 days, then 2, 3, and 4 months after the injections, and then every 2 months for 2 years. After that, you will be asked to return to the clinic every 4 months for the rest of your life. At each visit, the following tests and procedures will be performed:

* You will be asked to give information about any new medications and therapies, including vitamins, herbs, and supplements that you may be taking.
* You will be asked to describe any changes in your health or how you feel.
* You will have a neurological exam.
* Your weight will be measured on Day 28 and at 2, 3 and 4 months.
* Your vital signs will be measured.
* You will be asked to provide a blood sample (about 1 teaspoon), a urine sample and a swab of your nose and throat will be taken.
* You will have blood tests (about 4 teaspoons) to evaluate your clinical status on Days 4, 7, 28, and at 2, 3 and 4 months.
* Blood (about 2 teaspoons) will be collected to look for the presence of anti-AD5 and virus.
* Women who are able to become pregnant must have a blood (about 1 teaspoon) pregnancy test on 1 and 4 month visit and all follow-up visits after that.
* You will have an MRI at each visit except for Day 4.
* After the 4 month visit, you will have an evaluation to see how you have responded to treatment for the first 2 years and every 4 months after that.

Group B Follow-up Visits:

You will be seen in the study center for check-ups on Days 4, 7, and 13 after the injection but before your craniotomy. At each visit the following tests and procedures will be performed:

* You will be asked to give information about any new medications and therapies, including vitamins, herbs, and supplements that you may be taking.
* You will be asked to describe any changes in your health or how you feel.
* You will have a neurological exam.
* Your vital signs will be measured.
* You will be asked to provide a blood sample (about 1 teaspoon), a urine sample and a swab of your nose and throat will be taken.
* You will have a blood test (about 4 teaspoons) to evaluate your clinical status.
* Blood (about 2 teaspoons) will be collected to look for the presence of anti-AD5 and virus.
* Women who are able to become pregnant must have a blood (about 1 teaspoon) pregnancy test on Day 13, 1 and 4 month visits and all follow-up visits after that.
* You will have an MRI on Days 7 and 13 only.

If you are feeling well 14 days after the first injection of study drug, you will be brought back to the operating room for a second procedure to remove the tumor. You will undergo a craniotomy, in which the skull over the tumor is removed to get to the brain and tumor. The neurosurgeon will try to remove the tumor as completely as possible with the catheter tip from the first procedure in place. After the tumor has been removed, you will receive another dose of DNX-2401 that will be injected into the brain tissue that surrounded the tumor to try to kill any remaining tumor cells. This is called "Stage 2." The skull will then be replaced and the skin closed. Within 6 hours of the craniotomy on Day 14, you will have a neurological exam and your vital signs will be measured.

On the day of resection, a sample of the removed brain tumor tissue will be collected and stored until the study is over. Analysis of the tissue will be performed to look for the presence and activity of the virus, as well as any additional tests that are necessary for protocol purposes.

Group B Follow-up Visits after Craniotomy:

After the surgery, you will be seen in the hospital or come back to the center on Days 15, 18, 21, 28, and 42, at 2, 3 and 4 months, and then every 2 months for 2 years. After that, you will be asked to come back every 4 months for the rest of your life. At each visit, the following tests and procedures will be performed:

* You will be asked to give information about any new medications and therapies, including vitamins, herbs, and supplements that you may be taking.
* You will be asked to describe any changes in your health or how you feel.
* You will have a neurological exam.
* Your weight will be measured on Day 28, 42 and at 2, 3 and 4 months only.
* Your vital signs will be measured.
* You will be asked to provide a blood sample (about 1 teaspoon), a urine sample, and a swab of your nose and throat.
* You will have a blood test (about 4 teaspoons) to evaluate your clinical status.
* Blood (about 2 teaspoons) will be drawn to look for the presence of anti-AD5 and virus.
* Women who can become pregnant must have a blood (about 1 teaspoon) pregnancy test at all visits except Day 15 and 18.
* You will have an MRI.

For participants who are clinically unable to wait 14 days for surgery because of the tumor's size and/or location, or because they are experiencing serious neurological symptoms, the study chair may decide to skip the biopsy.

Group B Follow-up Visits (Stage 2--Craniotomy Only):

After the surgery, you will be seen in the hospital or come back to the center on Days 1, 4, 7, 14, and 28; at 2, 3, and 4 months; and then every 2 months for 2 years. After that, you will be asked to come back every 4 months for the rest of your life. At each visit, the following tests and procedures will be performed:

* You will be asked to give information about any new medications and therapies, including vitamins, herbs, and supplements that you may be taking.
* You will be asked to describe any changes in your health or how you feel.
* You will have a neurological exam.
* Your weight will be measured on Day 28 and at 2, 3, and 4 months.
* Your vital signs will be measured.
* You will be asked to provide a blood sample (about 1 teaspoon), a urine sample, and a swab of your nose and throat.
* You will have a blood test (about 4 teaspoons) to evaluate your clinical status.
* Blood (about 2 teaspoons) will be drawn to look for the presence of anti-AD5 and virus.
* Women who can become pregnant must have a blood (about 1 teaspoon) pregnancy test on 1- and 4-month visit and all follow-up visits after that.
* You will have an MRI.

This is an investigational study. At this time, DNX-2401 is only being used in research. Up to 96 patients will take part in this study (up to 48 in Group A and 48 in Group B). All will be enrolled at MD Anderson.

DNX-2401 (Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas

Phase I Trial of Conditionally Replication-Competent Adenovirus (DNX-2401, Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas

Each cohort of three subjects each sequentially assigned to escalating doses of DNX-2401, with acceptable grade of neurotoxicity Common Toxicity Criteria (CTC) \< grade 3, related to the study drug, and according to standard Gehan phase I dose-escalating criteria for toxicity.

DNAtrix, Inc.

Patients who will receive target therapy( Bevacizumab) for recurrent malignant gliomas will be asked to participate in this study. The routine sequences, Gd- enhanced MR imaging and APT MR imaging will be performed before and after target therapy.

Patients who will receive target therapy( Bevacizumab) for recurrent malignant gliomas will obtain routine sequences, Gd- enhanced MR imaging and APT MR imaging will be performed before and after target therapy. We will observe the change of tumor after target therapy using APT imaging. We will compare the change of tumor between Gd-enhanced and APT Imaging before and after therapy.

APT MR Imaging

Zhibo Wen, Doctor

Xianlong Wang, Master

Xiaoxiao Wu, Master

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.

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.

Biospecimen obtained by sugery or biopsy should be retained and test by pathology

The Efficacy of APT Magnetic Resonance Imaging in Predicting the Efficacy of Bevacizumab in Recurrent Malignant Gliomas

Clinical Study on the Efficacy of Amide Proton Transfer Magnetic Resonance Imaging in Predicting the Efficacy of Bevacizumab in Recurrent Malignant Gliomas

Observe the change of signal intensity of tumor on APT MR imaging before and after therapy, determine the predictive value of APT imaging about the efficacy of Bevacizumab in recurrent malignant gliomas.

Observe the change in dimension of recurrent tumor on Gd-enhanced MRI

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma	NCT00595322	Brain Cancer Recurrent Malig... Primary Brain T...	bevacizumab and...	18 Years -	Memorial Sloan Kettering Cancer Center
Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma	NCT00595322	Brain Cancer Recurrent Malig... Primary Brain T...	bevacizumab and...	18 Years -	Memorial Sloan Kettering Cancer Center
DNX-2401 (Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas	NCT00805376	Brain Cancer Central Nervous...	DNX-2401 Tumor Removal	18 Years -	DNAtrix, Inc.
Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma	NCT00595322	Brain Cancer Recurrent Malig... Primary Brain T...	bevacizumab and...	18 Years -	Memorial Sloan Kettering Cancer Center
The Efficacy of APT Magnetic Resonance Imaging in Predicting the Efficacy of Bevacizumab in Recurrent Malignant Gliomas	NCT03180697	Diagnoses Disea... Glioma of Brain	APT MR Imaging	18 Years - 80 Years	Zhujiang Hospital

Spots Global Cancer Trial Database for recurrent malignant gliomas