Nilotinib for Giant Cell Tumor

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nilotinib, a drug typically used for leukemia, can halt the growth or improve symptoms of pigmented villonodular synovitis (PVNS), a joint condition. The study targets individuals with PVNS that cannot be surgically removed or has progressed in the past year. Those who have received other treatments but not specific inhibitors for this condition may qualify to participate. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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 there any evidence suggesting that nilotinib is likely to be safe for humans?

Research shows that nilotinib is generally safe for people. Long-term studies indicate that it remains safe over time, with no deaths reported during treatment. Some patients have experienced side effects, but earlier research anticipated these.

Nilotinib is already approved for treating certain types of leukemia, establishing a known safety record. Although this study explores its use for a different condition, the existing safety data is reassuring. However, joining any clinical trial involves understanding potential risks, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nilotinib is unique because it targets the specific pathways involved in the growth of giant cell tumors. Unlike traditional treatments for giant cell tumors, such as surgery or radiation, Nilotinib is a tyrosine kinase inhibitor. This means it works by blocking certain enzymes that promote tumor growth, offering a more targeted approach. Researchers are excited about Nilotinib because it has the potential to provide an effective treatment option with fewer side effects compared to more invasive conventional therapies.

What evidence suggests that nilotinib might be an effective treatment for PVNS?

Research has shown that nilotinib is already used successfully to treat leukemia, a type of blood cancer. It blocks a protein that aids tumor growth. In studies with patients having conditions similar to pigmented villonodular synovitis (PVNS), such as tenosynovial giant cell tumor (TGCT), nilotinib slowed the disease. However, about half of the patients required additional treatment over time. This trial will evaluate nilotinib's potential to stop or slow the growth of PVNS. ^{1 3 6 7 8}

Who Is on the Research Team?

Andrew Wagner, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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

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

Negative urine or serum pregnancy test within days of start of study drug administration for women of childbearing potential

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922003793

Long-term follow-up of nilotinib in patients with advanced ... This long-term analysis of nilotinib for advanced D-TGCT showed that about half of the patients had progression and underwent additional treatment after 8.5 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35932628/

Long-term follow-up of nilotinib in TGCT This long-term analysis of nilotinib for advanced D-TGCT showed that about half of the patients had progression and underwent additional treatment after 8.5 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01261429

NCT01261429 | Study of Nilotinib Efficacy in Pigmented ... The purpose of this study is to explore the efficacy of nilotinib as a treatment of patients with progressive or relapsing pigmented villo-nodular synovitis ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11721949/

Real-world drug utilization and treatment patterns in patients ... This database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world.

5. novartis.com novartis.com/us-en/news/media-releases/longer-term-phase-iii-data-show-novartis-drug-tasigna-continues-surpass-gleevec-slowing-disease-progression-patients-newly-diagnosed-cml

Longer-term Phase III data show Novartis drug Tasigna® ... Longer-term Phase III data show Novartis drug Tasigna® continues to surpass Gleevec® in slowing disease progression in patients with newly diagnosed CML.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5452069/

Efficacy and safety of nilotinib in patients with KIT-mutated ... Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential ...

7. ema.europa.eu ema.europa.eu/en/documents/scientific-discussion/tasigna-epar-scientific-discussion_en.pdf

Tasigna, INN-nilotinib To determine if nilotinib treatment would be able to prolonged survival, 75 mg/kg/day nilotinib was orally administered to a larger cohort of mice over a 16-day ...

8. ashpublications.org ashpublications.org/bloodadvances/article/7/23/7279/497976/The-long-term-efficacy-and-safety-of-nilotinib-in

The long-term efficacy and safety of nilotinib in pediatric ... The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ∼5 years) ...