Nilotinib + Radiation for Chordoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Tyrosine kinase inhibitors, CYP3A4 inhibitors

Disqualifiers: Cardiac, Pancreatic, Liver, Renal, others

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

Compensation: Varies

Number of Visits: 2

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The study drug, Nilotinib, is believed to slow down tumor growth by regulating a gene involved in cellular growth of chordoma cells. During this research study, subjects will also receive radiation therapy which is considered a standard treatment for advanced chordomas. It is hoped by adding nilotinib, the benefits of radiation therapy can be enhanced without adding significant toxicities. The purpose of this research study is to determine the safety of nilotinib when used in combination with radiation therapy, and the highest dose of nilotinib that can be given safely with radiation therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently receiving treatment with strong CYP3A4 inhibitors or require anticoagulation with coumadin.

What data supports the effectiveness of the drug Nilotinib combined with radiation therapy for treating chordoma?

Nilotinib is being studied for its safety and feasibility in combination with radiation therapy for high-risk chordoma, as it targets specific growth factor receptors involved in tumor growth. While direct evidence for this combination is limited, similar drugs like imatinib and erlotinib have shown some effectiveness in treating chordoma, suggesting potential for targeted therapies. ^{1 2 3 4 5}

Is the combination of Nilotinib and Radiation safe for humans?

A Phase 1 study was conducted to determine the safety of combining Nilotinib with radiation therapy for high-risk chordoma, focusing on identifying the maximum tolerated dose and feasibility, indicating that safety evaluations are underway. ^{2 4 5 6 7}

How is the Nilotinib and Radiation treatment for Chordoma different from other treatments?

Nilotinib is a unique drug because it is a second-generation tyrosine kinase inhibitor, which means it blocks specific proteins that help cancer cells grow. This combination with radiation therapy is novel for Chordoma, as it may enhance the effectiveness of radiation by targeting cancer cell growth pathways, a strategy not commonly used for this condition. ^{8 9 10 11 12}

Research Team

Edwin Choy, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals with high-risk chordoma, a type of bone cancer. Participants must have a life expectancy over 3 months, be able to swallow capsules, and have measurable disease with proper organ function. It's not open to those who've had certain heart issues, are on strong CYP3A4 inhibitors or anticoagulants like coumadin, have gastrointestinal problems affecting drug absorption, acute pancreatitis, CNS infiltration by cancer cells, another primary cancer needing treatment, recent major surgery without recovery or investigational agent use within the last month.

Inclusion Criteria

My cancer is confirmed to be chordoma through tissue examination.

Measurable disease

My condition is considered high risk.

Exclusion Criteria

I haven't had major surgery in the last 4 weeks or I've recovered from it.

Treatment with other investigational agents within 30 days of Day 1

I have another cancer that needs treatment through the bloodstream.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Nilotinib Treatment

Participants receive nilotinib orally daily for 2 weeks before starting radiation therapy

2 weeks

1 visit (in-person)

Radiation Therapy

Participants receive daily radiation therapy concurrently with nilotinib until Day 56

6 weeks

Daily visits (in-person)

Extended Radiation Therapy

If surgery is not possible, an additional 3 weeks of radiation therapy is applied

3 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with tumor assessments every 6 months for one year, then annually

2 years

Regular visits (in-person)

Treatment Details

Interventions

• Nilotinib
• Radiation therapy

Trial Overview The study tests Nilotinib combined with radiation therapy in treating advanced chordomas. Nilotinib is believed to slow tumor growth by targeting specific genes in the tumor cells. The goal is to find out how safe this combination is and the highest dose of Nilotinib that can be given safely alongside standard radiation treatments.

Participant Groups

Group I: Nilotinib/XRT Experimental Treatment 2 Interventions

Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily radiation therapy until completion of radiation therapy. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.

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

Approved in European Union as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in United States as Tasigna for:

• Chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adult patients resistant to or intolerant to prior therapy that included imatinib

Approved in Canada as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Japan as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Switzerland as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

References

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

Chordoma: A Case Report and Review of Literature. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Response to erlotinib in a patient with treatment refractory chordoma. [2018]

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

Sustained response of a clivus chordoma to erlotinib after imatinib failure. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Synergistic drug combinations and machine learning for drug repurposing in chordoma. [2021]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Clinical Outcome of Sacral Chordoma Patients Treated with Pencil Beam Scanning Proton Therapy. [2021]

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

Conformal rotation therapy with central axis beam block is a feasible alternative to intensity-modulated radiotherapy for chordomas of the cervical spine. [2019]

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

Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation (WBRT) and Erlotinib treatment in patients with non-small cell lung cancer (NSCLC) with brain metastasis. [2015]

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

Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic options for treating brain metastases in non-small cell lung cancer. [2018]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Nilotinib, A Tyrosine Kinase Inhibitor, Suppresses the Cell Growth and Triggers Autophagy in Papillary Thyroid Cancer. [2022]