Nivolumab + stereotactic radiosurgery

Clinical trial of nivolumab with or without stereotactic radiosurgery in treating patients with recurrent, advanced, or metastatic chordoma

Summary

Doctors at Johns Hopkins Hospital are enrolling chordoma patients in a Phase 1 clinical trialResearch 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. studying the safety and initial effectiveness of the immunotherapySystemic therapies that are designed to teach the immune system how to find and destroy cancer cells. drug nivolumab with and without stereotactic radiosurgeryA type of external beam radiation that uses special equipment to position a patient and precisely deliver radiation to tumors in or near the brain, over a small number of treatments. (SRS). The goal of these therapies is to harness the body’s own immune system to more effectively fight chordoma.

This research study is designed specifically for chordoma patients 15 years or older with recurrent or metastatic tumors. The primary goal of this research study is to determine the safety of nivolumab alone or in combination with SRS for treating chordoma. The secondary goal is to determine whether these therapies can shrink or stop the growth of chordoma tumors. Dr. Lawrence Kleinberg is the Principal Investigator at Johns Hopkins Hospital.

Why this trial is being done

The immunotherapy drug nivolumab helps the immune system destroy tumor cells by blocking proteins called immune checkpoint molecules that cancer cells use to avoid attack by the immune system. Known as a “checkpoint inhibitor,” nivolumab is currently approved to treat several tumor types including melanoma, kidney cancer, lung cancer and bladder cancer. Recent laboratory research has shown that chordomas produce the same checkpoint molecules as these cancers, suggesting that a checkpoint inhibitor such as nivolumab might also be able to help the immune system more effectively fight chordoma. This research study is the first to test a checkpoint inhibitor for the treatment of chordoma.

One group of participants in this study will receive nivolumab alone, which is intended to stimulate the immune system to attack the tumor. A second group will receive nivolumab in combination with stereotactic radiosurgery (SRS). SRS, which delivers a high dose of focused radiation to a tumor over a short period of time, is already a standard treatment that is used to help control advanced or metastatic chordoma tumors (it is sometimes called CyberKnife or Gamma Knife, which are the names of machines used to deliver the radiation). Doctors believe SRS triggers an immune response by causing tumor cells to burst, exposing their abnormal contents to the immune system. It may also make tumor cells more sensitive to being killed by the immune system.

This understanding has provided rationale for testing the combination of checkpoint inhibitors with SRS. Clinical trials testing this combination in other tumor types have shown preliminary evidence of enhanced activity against the tumor compared with SRS alone or a checkpoint inhibitor alone. More recently, researchers at Johns Hopkins University showed that this combination reduces tumor growth and improves survival in a mouse model of chordoma. Taken together, this evidence provides strong rationale for a clinical trial testing nivolumab alone and in combination with SRS.

Who can participate

This study is designed specifically for chordoma patients whose tumors have come back in the same area or have spread to other parts of the body. Patients must meet the following basic criteria to be eligible:

Confirmed diagnosis of chordoma
Recurrent or metastatic diseaseWhen tumors have spread to other parts of the body from the original tumor site. confirmed by imaging (cannot be newly diagnosed, primary chordoma)
Age 15 years or older
No major laboratory abnormalities
No prior use of an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody
Eligible to receive radiation to site of tumor or metastasis
Willing and able to travel to the study site (Johns Hopkins Hospital in Baltimore) for all treatment and follow-up visits

Full eligibility criteria can be found on ClinicalTrials.gov.

How the trial will work

Participants are assigned to one of two treatment groups:
- Participants in the first group will receive nivolumab by IV over 30 minutes on day 1, and again every 2 weeks for about 4 months (8 doses). Beginning with dose 9, participants will receive nivolumab every 4 weeks at a higher dose.
- Participants in the second group will receive the same schedule of nivolumab treatments, plus stereotactic radiosurgery treatment on day 8.
The trial doctor will determine during the enrollment process which group is the best fit for each new participant.
A check-up exam will be performed at each visit, before participants receive the scheduled nivolumab treatments.
Patients can remain on the trial up to 2 years, or until there is disease progression or unacceptable side effects are experienced.
Participants will be evaluated for side effects for 100 days after stopping treatment. MRIs will be performed approximately every 10 weeks for 2 years, as part of standard follow-up.
All exams, treatments, and evaluations are provided at the trial site where the patient enrolled in the study. Participants not local to the trial sites MUST be willing and able to travel to their trial site for all visits required by the trial.

How to enroll in this trial

The trial team will need to review your medical history in order to determine if you are eligible to enroll. See the FAQ below, “How do I find out if I’m eligible to participate?”, for more specific information on the enrollment process.

FAQs

How much does it cost to participate?

Nivolumab will be provided at no cost to study participants. Participants and their insurance will be responsible for the cost of stereotactic radiosurgery, infusion costs, as well as any exams and tests required by the study. The new patient office of the study site will help you determine your insurance coverage for clinical trials.

Any other medical care needed while enrolled in the trial will be the responsibility of the participant or the participant’s insurance. Participants from out of town are responsible for any travel or lodging expenses necessary to make the required clinic visits every 2 or 4 weeks. Study sites may partner with local hotels to provide discounted rates to out-of-town patients.

What are the downsides of participating in the trial?

Side effects are possible from both immunotherapy and stereotactic radiosurgery. Talking with your doctor or the trial investigators is the best way to learn about the risks of participating in clinical trials.

How do I find out if I'm eligible to participate?

The trial team will need to review your medical records to determine if you are eligible.

For patients wishing to enroll at Johns Hopkins:

Patients within the U.S. should contact the Johns Hopkins new patient referral office at 410-955-8964 to request instructions on how to submit your medical records. Before calling, take a moment to review this page to learn what information to have on hand when you call the new patient referral office.
International patients should contact Johns Hopkins Medicine International at +1 410-502-7683. Visit their web page for more information.
Once you have submitted your medical records, please contact the trial nurse, Whitney Webb, RN, MSN at wwebb10@jhmi.edu to make an appointment.

Why do some participants in this study receive radiation and others don't?

Phase 1 trials are conducted to determine the safety of a treatment or treatment combination. Some participants will receive nivolumab alone and others will receive nivolumab plus radiation so that the safety of each of these can be determined.

What type of radiation is used in the trial?

Participants assigned to the second treatment group will receive stereotactic radiosurgery (SRS), which is a standard treatment for patients with recurrent or advanced chordoma. SRS involves delivering a high dose of focused radiation to the tumor in a single session, or small number of sessions, rather than conventional dosing over multiple weeks. Delivering the radiation in a small number of sessions (“”) may help protect healthy tissues surrounding the tumor from being damaged by the radiation, while also helping to stimulate a heightened immune response to the tumor. SRS is sometimes called CyberKnife or Gamma Knife as these are the names of two different machines that can be used to deliver the radiation dose.

How effective is nivolumab without radiation?

It is not currently known how effective nivolumab is for the treatment of chordoma. One of the goals of this study is to determine whether participants respond to nivolumab alone.

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

Even if you’ve had prior radiation you may be able to participate. This will depend on the dose and location of your previous radiation compared with the location of the current tumor. If you are not able to have more radiation, you may be able to join the trial as part of the group of participants who are only receiving nivolumab. Talk with the study doctor or nurse to learn more about whether you are eligible.

How is the treatment given?

For participants assigned to the first treatment group, nivolumab is given in 30 minute sessions once every 2 weeks for the first four months (8 doses), and then once every 4 weeks at a higher dose beginning with dose 9. Participants assigned to the second treatment group receive the same schedule of nivolumab treatments, plus stereotactic radiosurgery (SRS), which is performed only once, approximately 7 days after the first nivolumab treatment.

How long will I be in this study?

You will receive nivolumab treatments every 2 or 4 weeks for up to 2 years or until your tumor grows or you experience intolerable side effects. You will be evaluated for side effects for 100 days after stopping treatment. You will return for follow-up evaluation every 10 weeks thereafter for 2 years.

What check-ups are involved during the study?

Regular check-ups are done at your trial site every 2 or 4 weeks, on the same schedule as the nivolumab treatments. You will visit with the doctor for a check-up before beginning the 30-minute nivolumab infusion. You will also check-in with the doctor at your trial site after completion of the study, and every 10 weeks after that for 2 years.

I don't live near the trial site in Baltimore. Can I still participate?

All exams, treatments, and evaluations are provided at the trial site where the patient is enrolled. Patients not local to the trial sites MUST be willing and able to travel to their site for all visits required by the study. Travel and lodging expenses are the responsibility of the patient.

If you cannot afford to travel to the trial site for the required visits, financial assistance may be available from the Lazarex Cancer Foundation.

You may also be able to receive nivolumab outside of this trial if your doctor prescribes it off-labelThe practice of prescribing drug treatments that are not approved by government agencies to treat a particular disease. Doctors are allowed to prescribe drugs off-label if they believe it is in the best interest of the patient.; however, it is unlikely to be covered by insurance.

If you are unable to participate in this trial, there may be other trials available to you. See our Clinical Trials Catalogue or contact a Chordoma Foundation Patient Navigator for more information.

What happens if I decide to leave the trial and stop taking the drug?

You always have the option to stop treatment on a clinical trial. If you decide to stop treatment, the study investigators would like to continue seeing you for follow up visits so that they can monitor side effects and understand how well the treatment worked.

What happens if my tumor grows while enrolled in the study?

Often immunotherapy causes tumors to swell before ultimately shrinking. This is called a pseudoprogression. If your tumor grows by more than 25% while you are enrolled in the study and does not shrink after 12 weeks, treatment will be stopped. You may then seek other treatment or participate in a different clinical trial.

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

eIRB application number: IRB00117650

Learn more about immunotherapy

How is Immunotherapy Used to Fight Cancer? From Dana-Farber Cancer Institute and Science Illustrated

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PD-1/PD-L1 Pathway: A Security Checkpoint

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Information from Bristol-Myers Squibb, the maker of nivolumab

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.

Nivolumab + stereotactic radiosurgery

Clinical trial of nivolumab with or without stereotactic radiosurgery in treating patients with recurrent, advanced, or metastatic chordoma

Summary

Why this trial is being done

Who can participate

How the trial will work

How to enroll in this trial

FAQs

Learn more about immunotherapy

Information from Bristol-Myers Squibb, the maker of nivolumab

Disclaimer

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