GI-6301 + radiation

Clinical trial of GI-6301 (yeast-brachyury vaccine) versus placebo in combination with radiotherapy in locally advanced, unresectable chordoma

Summary

Researchers at the National Cancer Institute in Bethesda, Maryland, are now enrolling patients in a Phase 2 clinical trial evaluating whether a therapeutic vaccine called GI-6301 given in combination with radiation is more effective than radiation alone in causing tumor regression or preventing tumor progression.

The trial is designed specifically for chordoma patients 18 years and older with inoperable tumor, residual tumor following surgery, or locally recurrent tumor who are planning to have radiation.

Why this trial is being done

Radiotherapy is a standard treatment option for chordoma patients with residual or inoperable tumor. However, the majority of chordomas that are not fully resected will eventually progress after radiation. Research in other cancers suggests that the combination of radiation plus therapies that stimulate the immune system can have powerful antitumor effects. Therefore, in this trial, researchers are seeking to determine whether stimulating the immune system to target chordoma in combination with radiation can cause tumor shrinkage and/or prevent further tumor growth to a greater degree than radiation alone.

Specifically, this trial will test the therapeutic vaccine GI-6301, which is designed to stimulate the immune system to attack chordoma. Therapeutic vaccines are meant to help the immune system fight disease more effectively, as opposed to prophylactic vaccines (like the flu shot) which help to prevent disease. GI-6301 works by generating immunity against a protein called brachyury, which is found on most chordoma tumors but is absent from nearly all normal tissues. In other words, GI-6301 trains the immune system to attack chordoma but not healthy parts of the body.

A recently completed Phase 1 trial of GI-6301 demonstrated that the vaccine could be delivered safely. It also showed that the vaccine was capable of inducing immune responses against brachyury in chordoma patients. Of the eight chordoma patients whose tumors were growing when they entered the Phase 1 trial, five stopped growing and one shrunk by more than 30 percent while in the study.

Who can participate

The trial is designed specifically for chordoma patients who are at high risk of tumor regrowth following radiation, including:

Patients who have residual tumor remaining after surgery
Newly diagnosed patients who are unable to have surgery
Patients who have a local recurrence following previous surgery

Patients must meet the following basic criteria to be eligible:

Confirmed diagnosis of chordoma
Localized (no evidence of metastases) and inoperable tumor
Age 18 years or older
At least 1cm of tumor measurable on imaging
Able to receive at least 50 GyE of radiation to the tumor
No major laboratory abnormalities
No history of autoimmune disease
No allergy to yeast
Willing and able to travel to the National Cancer Institute (NCI) in Bethesda, MD for treatment and follow-up visits

Full eligibility criteria can be found on clinicaltrials.gov and on the NCI website.

How the trial will work

The trial is taking place at the National Institutes of Health Clinical Center in Bethesda, MD. The NCI will pay for transportation costs (including airfare) within the US and a portion of lodging costs for patients enrolled in this trial.

Participants in the trial will initially be randomized to receive radiation plus the vaccine, or radiation plus a blinded placebo. Those who receive radiation plus placebo will have the option to “cross-over” and begin receiving the vaccine if their tumor grows while on the study. This means that everyone who enters the study will be given the opportunity to receive the vaccine if radiation alone is not stopping the growth of the tumor.

The process of participating in the trial is as follows:

Patients travel to NIH to receive injections of the vaccine (or placebo) every 2 weeks for 3 doses prior to starting radiation (approximately 4 weeks).
Patients then complete radiation treatment with their home radiation oncologist (typically over a 1-2 month timespan).
Following completion of radiation, patients travel back to NIH to resume injections every 2 weeks for 3 more doses (approximately 6 weeks).
Doses then spread out to every 4 weeks for 4 doses, and then 1 dose every 3 months. This schedule is continued until disease progression.

Between all doses of vaccine, patients may return home and travel back for the next visit. There is no requirement to stay locally in Bethesda at any point in the study outside of clinic visits and dosing days.

Repeat imaging studies will be performed about 3 months after completion of radiation and then every 3 months for the first year, every 6 months for the second year, and yearly thereafter. Scans can be done earlier if new symptoms develop between scheduled scans.

How to enroll

To enroll in this study, patients or their doctors can contact the principal investigator, Deric Park, MD, at deric.park@nih.gov, or Christine Bryla, RN, at brylacm@mail.nih.gov.

FAQs

How do I find out if I’m eligible for this trial?

To find out if you are eligible for this trial, speak with your doctor or contact the study coordinator, Christine Bryla, RN, at brylacm@mail.nih.gov or (240) 760-6007. You can also find detailed eligibility criteria at ClinicalTrials.gov and on the NCI website.

What are the downsides of participating in the trial?

(1) You will have to travel to Bethesda, Maryland for all visits on the study.

(2) You may have side effects from the vaccine. The most likely side effects are mild and include fever, flu-like symptoms, and injection site reactions.

(3) You will not be able to participate in other clinical trials or receive any other systemic therapy while on this trial.

(4) Talking with your doctor or the trial investigator is the best way to learn more about the risks of participating in this or other clinical trials.

Is there a risk in delaying radiation to get the initial doses of vaccine?

The answer to this question is currently not known, but the doctors involved in this study believe it is very unlikely that waiting 6–8 weeks to start radiation would affect your long-term outcome. Patients often must wait for that period of time or longer to have radiation after surgery to allow for healing. Please ask your treating radiation oncologist for his or her opinion on this question before enrolling in this trial.

How effective is radiation without the vaccine?

Radiation is the standard treatment option for patients with residual or inoperable tumor. Radiation is excellent at controlling disease growth locally, in most cases for at least 3 years, and often longer. However, it is very uncommon for tumors to shrink with radiation alone, and most will eventually grow. This study has been designed to see if adding the vaccine will increase the benefit of radiation both on shrinking the disease and long-term outcomes, such as length of time until tumor growth (locally or in other sites of the body).

Can I participate in the trial if I have already had radiation?

Prior radiation does not keep you out of the trial, but you must meet all the eligibility criteria described above. If you have had prior radiation, you can participate as long as you have localized disease and your radiation oncologist believes that he or she can treat you with the required dose of radiation to that site.

What can I do if I've already had radiation?

Ask your radiation oncologist if you can be treated again with radiation to your current site of disease. If you can, you may be eligible, if you do not have metastatic disease. The dose of radiation you receive must be within certain limits, which your radiation oncologist and the NIH team will discuss.

Is the cost of my radiation treatment covered as part of the study?

In most situations, the answer will be no. The NIH Clinical Center does have a radiation oncology department, but in most cases, they will not have the necessary equipment to deliver the required doses of radiation. You should plan on having your radiation with an outside radiation oncologist who has experience treating chordoma. As a result, the NIH cannot pay for your radiation treatments; however, your insurance may cover these costs. In the unlikely event that your radiation can be delivered at NIH, there would be no cost for treatment.

Can I participate in the trial if I've had a complete resection?

No. To participate, your tumor has to be measurable on imaging. That means that at least 1 cm of tumor must be visible on an MRI or CT scan to be eligible for this study. This study is set up to evaluate the effect of the vaccine in combination with radiation. In order to do that, some tumor needs to be visible on scans so the investigators can determine if the combination of vaccine and radiation has caused the tumor to shrink. If there is no tumor to measure, they cannot evaluate the effect. Therefore, if you have recently had a complete resection and have no evidence of disease, you would not be eligible to participate. However, if you previously had a complete resection and now have regrowth, you could be eligible to participate.

How likely is my tumor to grow if I get radiation without the vaccine?

Recurrence rates with radiation alone are very low within 3–5 years. However, the risk of recurrence goes up with time and most patients eventually experience a recurrence at some point in the future. The hope is that the addition of the vaccine will decrease the likelihood of future growth and increase the likelihood of tumor shrinkage in the short term, but it is unknown whether the vaccine will improve the long-term outcome compared to radiation alone.

Aren't vaccines for preventing disease? How will a vaccine help if I already have chordoma?

Some vaccines are for preventing disease, but others, like this vaccine, are designed to treat disease. This type of vaccine is called a therapeutic cancer vaccine. That means it is intended to teach the immune system something about your cancer – in this case, that your cancer cells produce brachyury protein. Once the vaccine educates the immune system, immune cells will try to kill cells producing the brachyury protein, which is present in almost all chordoma cells.

How long can I continue getting the vaccine? Will this trial end at some point?

Currently, patients enrolled in the trial can continue getting the vaccine indefinitely as long as their tumor has not grown. After 2 years, the investigators may consider spacing the doses out even further (every 6 or 12 months). This will depend on results of the study up to that point, the availability of the vaccine, and whether you choose to continue. It is not known if vaccines for cancer need to be given in an ongoing fashion. If they are, there is reason to believe that they can be given further apart later than they would be given initially.

Why do I have to continue getting the vaccine?

It is not known for certain that you need to continue the vaccine, but it is believed that continuing to boost the immune system is likely to be beneficial.

For how long do I have to keep coming back to NIH?

Initially you will come every 2 weeks (beginning 4 weeks before radiation and ending 6 weeks after recovery from radiation). Then you will need to come every 4 weeks until you’ve received 4 doses of the vaccine. You will need to return once every 3 months for vaccine doses thereafter. This treatment will continue until evidence of disease progression. If your disease progresses and you learn that you had been receiving the placebo, you have the option to cross-over and receive the vaccine at that point.

What happens if I decide to stop taking the vaccine?

You always have the option to refuse treatment on a clinical trial. Even if you stop taking the vaccine, NIH would still like for you to return for scheduled follow-up visits so the study can generate useful information about how well this vaccine works. You are always welcome to refuse, but it will help researchers understand whether this vaccine works if you continue with the study as planned.

Why do some patients on the trial get a placebo?

In order to prove that a treatment works it must be compared to something. In this study, researchers at NIH have gone to great lengths to ensure that each participant is not being undertreated. Instead, all patients will be treated with the standard therapy, radiation. Half will receive the addition of vaccine; the other half will receive a blinded placebo. This is done so there will be no bias by the investigators about the outcome. This is the most useful and quickest way to determine if this vaccine works and whether it can be helpful to most chordoma patients. If you initially receive placebo you will have the option to cross-over and receive the vaccine if your tumor grows. This means you can get the vaccine, at some point in the study, no matter which group you are assigned to.

What are the chances of getting a placebo on the trial?

You have a 50% chance of being assigned to placebo (1 out of 2 chance).

When will I find out if I got the placebo?

You will not know, nor will your doctors at NCI know, if you are getting placebo while on the study. If your tumor begins to grow, your doctors will remove the “blinding” and find out if you were receiving placebo. If you were being given the placebo, you have the opportunity to receive the vaccine at that point if you wish.

What happens if my tumor grows while on the trial?

For the first year, your tumor will be measured, but growth will not take you off the trial unless you have new symptoms. Sometimes when immunotherapies are working they cause tumors to swell with inflammation before the tumor eventually shrinks. This is called a pseudo-progression. So, if your tumor grows in the short term it may actually mean that the treatment is working. After one year, if you have disease growth, you would have the study treatment stopped. If you were assigned to the placebo group, you would have the option to cross-over and receive the vaccine at that point.

How and when will I know if the vaccine is helping?

Your doctors at the NCI will go over each imaging scan with you at your check-up visits and let you know if your tumor is shrinking, staying the same, or growing. This is done every 3 months after radiation for the first year, every 6 months during the second year, and yearly thereafter. Imaging can also be done earlier if you have new symptoms. Any effect seen will be discussed with you, but it is important to note that your doctors at the NCI will not know if you are getting placebo or vaccine. If your tumor shrinks, it may be due to the combination of vaccine and radiation, but it also may be due only to the radiation. At the end of the study, results will be compared to determine if radiation and vaccine improved outcomes compared with radiation and placebo.

Are there any restrictions I'm going to have while on the trial?

You cannot take steroids during the study, except during radiation, if needed. Any new medications you plan to start should be discussed with the study team at NIH prior to the first dose of the new medication to ensure there are no conflicts with the study. Otherwise, there are no restrictions. The NIH team can work around scheduling conflicts for visits when possible.

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.

Contact a CF Patient Navigator

Learn more about immunotherapy

From the National Cancer Institute

From the Chordoma Foundation

Dr. Chris Heery discusses immune therapy at a Chordoma Community Conference

Dr. Peter Wettstein discusses immunotherapy for chordoma at a Chordoma Community Conference

Disclaimer

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.