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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding nilotinib, a medication believed to slow tumor growth, can enhance the effects of radiation therapy for chordoma, a rare cancer. The main goal is to determine the safest dose of nilotinib to use with radiation without causing serious side effects. Suitable participants have a confirmed chordoma diagnosis, consider their disease high-risk, and can swallow pills. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using nilotinib with radiation therapy is safe for patients with high-risk chordoma. Studies found that a 200 mg daily dose of nilotinib with radiation was generally well-tolerated. Although the long-term effects are still under investigation, serious heart-related side effects, such as changes in heart function, are rare. While this trial is in an early stage, past use of nilotinib suggests it can be safely combined with radiation without adding significant risk. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nilotinib offers a promising new approach for treating chordoma because it targets specific pathways involved in cancer cell growth that are not addressed by current treatments. Most standard therapies for chordoma rely primarily on surgery and radiation, but nilotinib is a tyrosine kinase inhibitor that works by blocking signals that promote tumor growth. Researchers are excited about its potential to enhance the effects of radiation therapy, potentially improving outcomes for patients who have limited options beyond traditional methods.

What evidence suggests that nilotinib combined with radiation therapy could be effective for chordoma?

Research has shown that using nilotinib with radiation therapy, the treatment combination under study in this trial, may help slow the growth of chordoma tumors. Specifically, patients who received this combination in studies had a median progression-free survival of about 58 months, meaning many experienced a delay in tumor growth for nearly five years. Additionally, the two-year overall survival rate was 95%, indicating a strong potential for extending life with this treatment. Nilotinib targets a specific gene that controls cell growth in chordoma tumors. ^{1 3 5 6 7}

Who Is on the Research Team?

Edwin Choy, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

Life expectancy > 3 months

Exclusion Criteria

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

I have another cancer that needs treatment through the bloodstream.

Treatment with other investigational agents within 30 days of Day 1

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30077789/

A Phase 1 Study of Nilotinib Plus Radiation in High-Risk ... The objective best response rate was 6% (1 of 18 patients, 95% confidence interval [CI], 0.1%-27%). The median progression-free survival was ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301618334710

A Phase 1 Study of Nilotinib Plus Radiation in High-Risk ... In this phase 1 clinical trial, patients with high-risk chordoma were treated with a combination of nilotinib plus radiation with or without surgical resection.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e23505

Updated 5-year local control (LC), metastasis-free survival ... The 4 and 5-year OS rates were 70.2% (95% CI 44.4-95.9) and 54.6% (95% CI 20.5-88.6). Conclusions: In updated data from a cohort of high-risk ...

4. researchgate.net researchgate.net/publication/326810063_A_Phase_1_Study_of_Nilotinib_Plus_Radiation_in_High-Risk_Chordoma

A Phase 1 Study of Nilotinib Plus Radiation in High-Risk ... The results of their study showed that the median PFS was 58.15 months, with a 2-year overall survival rate was 95% (24) .

5. withpower.com withpower.com/trial/phase-1-chordoma-7-2011-f15d2

Nilotinib + Radiation for Chordoma · Info for Participants The study drug, Nilotinib, is believed to slow down tumor growth by regulating a gene involved in cellular growth of chordoma cells.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01407198

Nilotinib With Radiation for High Risk Chordoma | ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3366654/

Clinical cardiac safety profile of nilotinib - PMC QT prolongation, changes in left ventricular ejection fraction, and clinical cardiac adverse events were uncommon in patients treated with nilotinib.