Nilotinib for Giant Cell Tumor

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Andrew J. Wagner, MD, PhD

Must not be taking: CSF1 inhibitors, CYP3A4 inhibitors

Disqualifiers: Cardiac, Pancreatic, Liver, Bleeding, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Continuous until disease progression or unacceptable toxicity

17 Participants Needed

Trial Summary

What is the purpose of this trial?

Nilotinib is a drug that is used to treat a form of a blood cancer called leukemia. Nilotinib works by blocking the action of a protein that might be important for the growth of pigmented villonodular synovitis (PVNS). In this research study the investigators are testing whether nilotinib can stop the growth of PVNS or improve the symptoms experienced from PVNS.

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

You may need to stop taking certain medications before joining the trial, especially if they are strong CYP3A4 inhibitors or medications that can prolong the QT interval. If you are on these medications, you might need to switch to different ones before starting the study drug.

Is nilotinib (Tasigna) generally safe for humans?

Nilotinib (Tasigna) is generally considered safe for humans, but it can cause side effects, some of which may be serious. Common side effects include low blood cell counts and mild to moderate non-blood-related issues. It has been used safely in patients with chronic myeloid leukemia, but monitoring for side effects is important. ^{1 2 3 4 5}

How is the drug Nilotinib different from other treatments for giant cell tumor?

Nilotinib is unique because it is a CSF1R inhibitor, which means it targets the overexpression of colony-stimulating factor-1, a key driver in giant cell tumors, offering a non-surgical option for patients who cannot undergo surgery. ^{6 7 8 9 10}

Research Team

Andrew Wagner, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with progressive pigmented villonodular synovitis (PVNS) or related tumors, who haven't responded to other treatments and can't have surgery. Participants need good organ function, a life expectancy over 6 months, measurable disease on scans, and must be able to perform daily activities with minimal assistance. They should not be pregnant or breastfeeding and must use contraception.

Inclusion Criteria

Life expectancy greater than 6 months

I can care for myself and am up and about more than 50% of my waking hours.

QTc less than or equal to 450 ms on 12-lead ECG

Exclusion Criteria

I cannot undergo MRI scans due to health reasons.

I have not taken drugs like nilotinib or imatinib for a giant cell tumor.

I have liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nilotinib 400 mg twice daily in 4-week cycles. Clinic visits on Days 1 and 8 of the first cycle, and Day 1 of subsequent cycles.

Continuous until disease progression or unacceptable toxicity

Cycle 1: 2 visits (in-person), Subsequent cycles: 1 visit (in-person) every 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Nilotinib

Trial Overview The trial is testing Nilotinib's effectiveness against PVNS/tumors that are either growing back after treatment or spreading. It blocks proteins that may cause tumor growth. The study will see if it can halt tumor progression or relieve symptoms.

Participant Groups

Group I: Nilotinib Experimental Treatment 1 Intervention

Nilotinib 200 mg taken as 400 mg twice daily, continuously

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?

Andrew J. Wagner, MD, PhD

Lead Sponsor

Trials

1

Recruited

20+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Findings from Research

In a study of 54 patients with giant cell tumors (GCT) treated with 24 weeks of neoadjuvant denosumab therapy, significant improvements were observed in clinical symptoms, as indicated by reduced visual analogue scale (VAS) scores from a median of 7.0 to 2.0.

Histopathological outcomes also improved, with a notable reduction in the number of stromal cells per high-power field, showing a statistically significant decrease (p < 0.001), while tumor size and giant cell counts showed improvements without significant gender differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repercussions of Denosumab in Patients With Giant Cell Tumor of Bone: An Observational Study. Rath, BK., G, A., Mohanty, P., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

[Guidelines for the management of nilotinib (Tasigna)-induced side effects in chronic myelogenous leukemia: recommendations of French Intergroup of CML (Fi-LMC group)]. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Early and sustained deep molecular response achieved with nilotinib in high Sokal risk chronic myeloid leukemia patients. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Effects of nilotinib on single-dose warfarin pharmacokinetics and pharmacodynamics: a randomized, single-blind, two-period crossover study in healthy subjects. [2022]

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

Tasigna for chronic and accelerated phase Philadelphia chromosome--positive chronic myelogenous leukemia resistant to or intolerant of imatinib. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. [2022]

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

Long-term follow-up of nilotinib in patients with advanced tenosynovial giant cell tumours: Long-term follow-up of nilotinib in TGCT. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor. [2021]

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

Long term term follow-up of tyrosine kinase inhibitors treatments in inoperable or relapsing diffuse type tenosynovial giant cell tumors (dTGCT). [2020]

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

Repercussions of Denosumab in Patients With Giant Cell Tumor of Bone: An Observational Study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. [2020]