|First Submitted Date ICMJE||December 8, 2008|
|First Posted Date ICMJE||December 9, 2008|
|Last Update Posted Date||February 23, 2015|
|Start Date ICMJE||February 2009|
|Primary Completion Date||February 2015 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Maximum Tolerated Dose (MTD) DNX-2401 [ Time Frame: Assessed during 14 day waiting period between doses (every 28 days). ]
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.
|Original Primary Outcome Measures ICMJE
||To find the highest tolerable dose of DELTA-24-RGD-4C that can be injected directly into brain tumors and into the surrounding brain tissue where tumor cells can multiply. [ Time Frame: 13 Years ]|
|Change History||Complete list of historical versions of study NCT00805376 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE
||To study how the new drug DELTA-24-RGD-4C affects brain tumor cells and the body in general. [ Time Frame: 13 Years ]|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||DNX-2401 (Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas|
|Official Title ICMJE||Phase I Trial of Conditionally Replication-Competent Adenovirus (DNX-2401, Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas|
|Brief Summary||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.
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.
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.
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:
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:
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:
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:
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||February 2015|
|Primary Completion Date||February 2015 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00805376|
|Other Study ID Numbers ICMJE||ID01-310|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||DNAtrix, Inc.|
|Study Sponsor ICMJE||DNAtrix, Inc.|
|Collaborators ICMJE||Not Provided|
|PRS Account||DNAtrix, Inc.|
|Verification Date||February 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP