Nivolumab +/− Stereotactic Radiosurgery for Chordoma

Recruiting at 2 trial locations

Overseen By Jessica Wollett

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Chemotherapy, Investigational drugs, Immunosuppressants, others

Disqualifiers: Autoimmune disease, HIV, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or investigational drugs within 21 days before starting the trial, and you should not be on systemic steroids or immunosuppressive medications within 14 days of starting the study drug.

What data supports the effectiveness of the treatment Nivolumab +/− Stereotactic Radiosurgery for Chordoma?

Research suggests that chordoma may respond to immunotherapy, as seen in cases where patients with advanced chordoma showed positive responses to anti-PD1 antibodies, similar to Nivolumab. Additionally, stereotactic radiosurgery has been used to improve local control in various cancers, which may also benefit chordoma treatment. ^{1 2 3 4 5}

Is the combination of Nivolumab and Stereotactic Radiosurgery safe for humans?

There is no specific safety data available for the combination of Nivolumab and Stereotactic Radiosurgery in the provided research articles. ^{1 2 4 6 7}

How does the drug Nivolumab differ from other treatments for chordoma?

Nivolumab is unique for chordoma treatment because it is an immunotherapy drug that works by blocking a protein called PD-1, which helps the immune system recognize and attack cancer cells. This approach is different from traditional treatments like surgery and radiation, and it may offer a new option for patients whose tumors are resistant to conventional therapies. ^{1 2 3 4 8}

What is the purpose of this trial?

This phase I trial studies the side effects of nivolumab with or without stereotactic radiosurgery (SRS) in treating patients with chordoma that has come back or spread from where it started to other places in the body. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. It is not yet known whether giving nivolumab with or without stereotactic radiosurgery may work better in treating patients with chordoma.

Research Team

Lawrence Kleinberg, MD

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Eligibility Criteria

This trial is for adults with chordoma that has returned or spread, who can perform most daily activities (Karnofsky score >= 70%). They must have measurable disease progression and adequate organ function. Women of childbearing potential and sexually active men must use contraception. Exclusions include prior anti-PD-1/PD-L1 therapy, recent vaccines, certain previous treatments, active infections including HIV/hepatitis B/C, autoimmune diseases requiring steroids or immunosuppressants, pregnancy/breastfeeding, and inability to follow up.

Inclusion Criteria

My scans show my cancer has grown or spread.

I can provide details of my past cancer treatments and when my cancer progressed.

My kidney function tests are normal.

Exclusion Criteria

I have been cancer-free for at least 2 years, except for certain cancers.

I haven't taken steroids or immunosuppressants in the last 14 days.

My condition doesn't allow for the planned radiation treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab intravenously every 14 days for 8 doses, then every 28 days for a total of 2 years. In Arm II, patients also undergo stereotactic radiosurgery on day 8 of course 1.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 100 days and every 10 weeks thereafter.

Long-term

Treatment Details

Interventions

• Nivolumab
• Stereotactic Radiosurgery

Trial Overview The trial is testing the safety of nivolumab (a monoclonal antibody) alone or combined with stereotactic radiosurgery (SRS), a precise high-dose radiation treatment targeting tumors with minimal damage to surrounding tissue. The goal is to see which approach better inhibits tumor growth in recurrent or metastatic chordoma.

Participant Groups

Group I: Arm II (nivolumab, SRS) Experimental Treatment 3 Interventions

Patients receive nivolumab as in Arm I. Patients undergo stereotactic radiosurgery (SRS) as per standard of care on day 8 of course 1.

Group II: Arm I (nivolumab) Experimental Treatment 2 Interventions

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 14 days for 8 doses, then every 28 days for a total of 2 years in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Chordoma Foundation

Collaborator

Trials

4

Recruited

100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase 1 Study of Nilotinib Plus Radiation in High-Risk Chordoma. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

First report of clinical responses to immunotherapy in 3 relapsing cases of chordoma after failure of standard therapies. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic implications of CD8+/Foxp3+ ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Clinical outcomes and toxicities of 100 patients treated with proton therapy for chordoma on the proton collaborative group prospective registry. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum. [2019]