MVA-BN-Brachyury + FPV-Brachyury vaccines
A Phase 2 trial of BN-Brachyury and radiation therapy in patients with advanced chordoma
Researchers at Massachusetts General Hospital and Mayo Clinic are enrolling patients in a Phase 2 Research studies involving human subjects that are done to test whether a treatment is safe, and how well it will work to treat a specific disease. that will determine whether a cancer treatment vaccine in combination with radiation can cause tumors to shrink in patients with advanced chordoma. The vaccine, called BN-Brachyury, is a prime-boost vaccine, meaning that the first vaccine doses “prime” the immune system response, and the following doses boost that response and make it stronger. This particular vaccine is designed to prompt the immune system to attack and kill cells that contain a protein called A gene that makes a protein, also called brachyury, that is present at high levels in nearly all chordoma tumors.. The brachyury protein is produced by chordoma tumor cells, but not by other healthy cells in the body. You can read more detailed information in the About the vaccine section below.
Patients who have locally advanced or metastatic tumors and are planning to have radiation are eligible to participate in this trial. The radiation plan must include a dose of radiation biologically equivalent to 1 The dose of radiation delivered during one session of radiation therapy. of 8 The abbreviation for gray equivalents, which refers to the unit of measurement for an absorbed dose of radiation. (this should be discussed with your Radiation Oncologist). All patients will have 3 doses of the vaccine before radiation treatment begins followed by additional vaccine treatments after radiation is complete. The study will determine how often the irradiated tumor shrinks when the vaccine is given compared to the results of previous studies when radiation was given alone. The trial is sponsored by Bavarian Nordic. The Principal Investigators are Dr. Greg Cote at Massachusetts General Hospital, Dr. Scott Okuno at Mayo Clinic Rochester, Dr. Steven Attia at Mayo Clinic Jacksonville, and Dr. Mahesh Seetharam at Mayo Clinic Scottsdale.
Why this trial is being done
Surgery and high-dose radiation are currently the main treatment options for chordoma. Radiation is also sometimes used instead of surgery when surgery would carry unacceptable risks. The chance of tumor growth after surgery is significantly higher for patients who do not have their tumor completely removed.
The goal of this trial is to determine if the vaccine therapy in combination with radiation can shrink chordoma tumors. In this study, patients will be treated with a therapeutic vaccine that stimulates the immune system to fight cancer cells. Research in other cancers suggests that radiation in combination with Systemic therapies that are designed to teach the immune system how to find and destroy cancer cells. can shrink tumors.
Who can participate
This trial is for patients with locally advanced chordoma or metastatic chordoma who are planning to have radiation. If more than one tumor is present, radiation may be given to one, some, or all tumor sites, as recommended by your radiation oncologist. If your tumor(s) will be removed with surgery, then you are not eligible.
To be eligible to enroll in this study, you must:
- Have a diagnosis of chordoma
- Have advanced or When tumors have spread to other parts of the body from the original tumor site. that cannot be cured by surgery
- Be able to receive the biologic equivalent of at least 8 Gy in a single fraction of radiation to one tumor site (you must talk with your Radiation Oncologist about this)
- Be willing and able to travel to your enrolling study site for all treatment and follow-up visits (full list of sites at ClinicalTrials.gov)
Full eligibility criteria can be found at ClinicalTrials.gov.
How the trial will work
The trial will take place in at least 4 leading medical centers in the United States. A list of the centers currently enrolling patients can be found at ClinicalTrials.gov. Travel costs may be covered up to a certain amount for trips to the center where you will participate. Please contact the center closest to you to find out details.
The process of participating in the trial is as follows:
- Patients receive vaccine injections every 2 weeks for 6 weeks. These doses may only be given at the medical center where the patient enrolled in the trial.
- Patients have radiation treatment, which can range from 1 day to 2 months, depending on the treatment plan. This can be done at any Radiation Oncology center as long as radiation requirements are met.
- When radiation is complete, patients receive vaccine injections every month for 4 months, then every 3 months for up to 2 years. At these visits, the patient’s tumor will also be scanned.
- Between all doses of vaccine, patients return home and then travel back to their trial site for the next visit. There is no requirement to stay locally besides when clinic visits and dosing days are scheduled.
- Imaging studies will be performed about 3 months after completion of radiation and then every 3 months for up to 2 years. Scans can be done earlier if new symptoms develop between scheduled scans.
How to enroll in this trial
To learn more about enrolling in the trial, please contact the person below at the site where you would enroll.
- Barbara Anderson, RN, MSN | (617) 643-2427 | Massachusetts General Hospital
- Jordana Whipkey | (507) 286-5027 | Mayo Clinic Rochester
- Katherine Sheffield | (904) 953-3972 | Mayo Clinic Jacksonville
- Ana Chinchilla Villalobos | (480) 342-3741 | Mayo Clinic Scottsdale
BN-Brachyury is comprised of two recombinant poxviral vectors to be used together in a prime-boost vaccination regimen. The priming vector is a highly attenuated, non-replicating vaccinia virus Modified Vaccinia Ankara-Bavarian Nordic-Brachyury (MVA-BN-Brachyury) and the boost is a recombinant fowlpox virus (FPV-Brachyury). The viruses are modified to include the A segment of genetic material that has a particular function. Humans have approximately 25,000 different genes. Every cell in the body has the same set of genes, however, different genes are turned on in different tissues, and at different times. for brachyury as well as molecules known to increase immune activation.
The priming dose (MVA) of this vaccine has been evaluated in 38 patients with advanced cancer. In that trial, the vaccine was well-tolerated with only one side effect deemed to be severe, which was diarrhea lasting less than 48 hours. Otherwise, the most common side effect was injection site reaction, which was usually mild or moderate. Other side effects were flu-like symptoms (in about 34 of 100 doses) and fever (in 18 of 100 doses), both of which resolved without other treatment within a few days. The vaccine induced brachyury-targeted immune responses in most patients (about 8 of every 10 patients in the highest dose levels tested).
Another study evaluated the priming (MVA) and booster (FPV) doses given to the same 11 patients. In that study, the vaccine was also well tolerated with similar adverse event profile to what was seen in the study of MVA-BN-Brachyury alone. To see if you can participate in this trial and for more information about this trial visit ClinicalTrials.gov.
If you have more questions about this trial or other clinical trials that may be options for chordoma patients, please contact a Chordoma Foundation Patient Navigator.
Learn more about brachyury
Medical information provided by the Chordoma Foundation in any medium is for informational and educational purposes only. After reading content from the Chordoma Foundation, review the information carefully with your physician. Information from the Chordoma Foundation is not a substitute for consultations with qualified health care professionals who are familiar with your medical conditions and needs. The Chordoma Foundation strongly recommends that care and treatment decisions be made in consultation with your physician or other qualified health care professionals who are familiar with your specific health situation.