Nilotinib for Preventing Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must be taking: Paclitaxel

Must not be taking: CYP3A4 inhibitors, OATP1B1 inhibitors

Disqualifiers: Metastatic disease, HER2+ with trastuzumab, others

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

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nilotinib (also known as Tasigna) can prevent nerve problems, such as numbness and tingling, that often occur in the hands and feet during chemotherapy for breast cancer. The study aims to determine the safest and most effective dose of nilotinib when combined with paclitaxel, a common chemotherapy drug. Participants should have stage I-III breast cancer and be eligible for paclitaxel treatment to qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as potent CYP3A4 inhibitors and potent OATP1B1 inhibitors, before starting nilotinib. If you are on these medications, you may need to switch to a different one or discontinue them safely.

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

Research has shown that nilotinib, a drug being tested to prevent nerve damage from chemotherapy, has some safety data from other studies. One study found that nilotinib helped prevent nerve problems in breast cancer patients receiving chemotherapy. The drug was generally well-tolerated, although some patients experienced side effects.

Nilotinib is already approved for certain conditions, indicating its safety in those cases. However, this current study is in an early stage, so researchers are still determining the best dose and closely monitoring safety. While there may be some side effects, the research aims to find a dose that reduces them.

Prospective participants should discuss potential risks and benefits with the research team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nilotinib is unique because it targets the prevention of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients, a common side effect of treatments like paclitaxel. Unlike existing medications that primarily focus on pain management after neuropathy sets in, nilotinib may help prevent the onset of these nerve-related symptoms. Researchers are particularly excited about nilotinib's potential to offer a proactive approach by using its specific mechanism to inhibit pathways associated with nerve damage, potentially reducing the incidence and severity of CIPN from the start.

What evidence suggests that nilotinib might be an effective treatment for preventing chemotherapy-induced peripheral neuropathy in breast cancer patients?

Research suggests that nilotinib might help prevent chemotherapy-induced peripheral neuropathy (CIPN), the numbness and tingling caused by chemotherapy drugs like paclitaxel. Recent early-stage research shows that nilotinib can reduce these symptoms by affecting specific pathways related to nerve damage from chemotherapy. In this trial, participants will receive varying doses of nilotinib alongside paclitaxel to evaluate its effectiveness in preventing CIPN. Although current findings are promising, researchers continue to study nilotinib's ability to prevent CIPN in humans. ^{6 7 8 9 10}

Who Is on the Research Team?

Nicole Williams, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for men and women with stage I-III breast cancer who are about to receive paclitaxel therapy. Participants must have certain blood cell counts within normal ranges, no severe heart or kidney issues, and agree to use contraception if they can have children. People with gastrointestinal problems affecting drug absorption, metastatic disease, unresolved severe side effects from past treatments (except hair loss), current pregnancy or breastfeeding, specific allergies to the drugs used in this study, uncontrolled illnesses that could affect participation, or those using certain other medications cannot join.

Inclusion Criteria

Your absolute neutrophil count is at least 1,500 per microliter of blood.

Your doctor thinks you can receive weekly or closely spaced doses of paclitaxel by itself.

Your ability to perform daily activities without help is not more than a little bit limited.

Exclusion Criteria

You have stomach or intestine problems that could make it hard for your body to absorb nilotinib.

You have cancer that has spread to other parts of your body.

You have had side effects from previous treatments that have not gotten better.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Paclitaxel is given weekly on days 1, 8, 15 of every 21 days, with nilotinib given orally on cycle 1 Days 7, 14 once a day 24 hours prior to the paclitaxel infusion and again 30 minutes prior to the paclitaxel infusion on days 8, 15.

3 weeks

Weekly visits for paclitaxel administration

Phase II Treatment

Patients are randomized to receive either nilotinib or placebo in combination with paclitaxel. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

Weekly visits for paclitaxel administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 3 and 6 months.

6 months

Follow-up visits at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib

Trial Overview The trial is testing whether nilotinib can prevent numbness and tingling caused by chemotherapy (specifically paclitaxel) in patients with early-stage breast cancer. It's a phase Ib/II study which means it's looking at the best dose of nilotinib for safety and effectiveness while also trying to find out how well it works for preventing nerve damage known as peripheral neuropathy.

How Is the Trial Designed?

Group I: Dose level 3 Experimental Treatment 4 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15. Patients also receive nilotinib hydrochloride monohydrate PO on days 7, 8, 14, and 15 of cycle 1 and days -1, 1, 7, 8, 14, and 15 of cycle 2. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Dose level 2 Experimental Treatment 4 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15. Patients also receive nilotinib hydrochloride monohydrate PO on days 7, 8, 14, and 15 of cycle 1 and days -1, 1, 7, 8, 14, and 15 of cycle 2. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Dose level 1 Experimental Treatment 4 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15. Patients also receive nilotinib hydrochloride monohydrate PO on days 7, 8, 14, and 15 of cycle 1 and days -1, 1, 7, 8, 14, and 15 of cycle 2. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 1313 patients with stage III colon cancer, a 3-month course of oxaliplatin-based chemotherapy significantly reduced the incidence of long-lasting peripheral sensory neuropathy (PSN) compared to a 6-month course (9.7% vs 24.3%).

The 3-month treatment duration did not compromise disease-free survival (DFS) outcomes, suggesting that a shorter course, particularly with the CAPOX regimen, may be a safer and effective option for patients, especially those with low-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. Yoshino, T., Yamanaka, T., Oki, E., et al.[2022]

In a study of 488 women receiving docetaxel or paclitaxel, 37.3% of dose-limiting chemotherapy-induced peripheral neuropathy (CIPN) events were attributed to paclitaxel, with a significantly higher incidence (16.1%) compared to docetaxel (2.4%).

Women who experienced dose reductions or treatment discontinuation due to CIPN received significantly less cumulative chemotherapy than planned, indicating that CIPN can impact treatment effectiveness and necessitates further investigation into its implications on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. Speck, RM., Sammel, MD., Farrar, JT., et al.[2022]

In a study of 126 women treated with taxane-based chemotherapy for breast cancer, 73% reported experiencing chemotherapy-induced peripheral neuropathy (CIPN), which significantly affected their quality of life and physical functioning.

CIPN severity was notably higher in Black or African American women, indicating a need for targeted screening and intervention strategies to address this disparity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice. Simon, NB., Danso, MA., Alberico, TA., et al.[2022]

Chronic sensory neuropathy in chemotherapy patients is influenced by complex interactions between cancer and chemotherapy, which affect neuronal excitability and inflammatory responses, as shown by global transcriptional profiling of dorsal root ganglia.

The study identified Kv3.3 potassium ion channels as a potential contributor to sensory neuron dysfunction, and revealed new behavioral deficits in forelimb placement that were not predicted by previous studies of chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy. Housley, SN., Nardelli, P., Carrasco, DI., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130796/

A Phase I Study of Nilotinib in Combination with Paclitaxel ... Recent preclinical data demonstrated that nilotinib attenuates paclitaxel-induced peripheral neuropathy (PIPN) via inhibition of the murine organic anion ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04205903?tab=results

Study Results | NCT04205903 | Nilotinib in Preventing ... Study Results | NCT04205903 | Nilotinib in Preventing Paclitaxel-Induced Peripheral Neuropathy in Patients With Stage I-III Breast Cancer | ClinicalTrials.gov.

3. withpower.com withpower.com/trial/phase-1-breast-neoplasms-11-2020-d68c7

Nilotinib for Preventing Chemotherapy-Induced Peripheral ... In a study of 126 women treated with taxane-based chemotherapy for breast cancer, 73% reported experiencing chemotherapy-induced peripheral neuropathy (CIPN), ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11978143/

Results of the preclinical multicenter randomized controlled ... Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and serious side effect of many cytotoxic drugs, including paclitaxel.

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT04205903/

Trial | NCT04205903 This study aims to test the safety and effectiveness, both good and bad, of taking nilotinib in preventing chemotherapy-induced peripheral neuropathy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6825524/

Recent developments of novel pharmacologic therapeutics for ... Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose limiting toxicity, negatively impacting both quality of life and disease outcomes.

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

Tasigna, INN-nilotinib - EMA Nilotinib is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A warning has been ...

8. scientificarchives.com scientificarchives.com/article/drug-induced-peripheral-neuropathy-focus-on-newer-offending-agents

Drug-Induced Peripheral Neuropathy: Focus on Newer ... Current evidence suggests that incidence rates for neuropathy vary by drug and cancer type, estimated at 10% for TKIs and 14% for ICIs. Increased vigilance is ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923007092

Chemotherapy-Induced Peripheral Neuropathy Chemotherapy-induced peripheral neuropathy (CIPN) is a serious and often persistent adverse consequence of certain chemotherapeutic agents.

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS12128

A phase Ib study of the safety and pharmacology ... A phase Ib study of the safety and pharmacology of nilotinib to prevent paclitaxel-induced peripheral neuropathy in patients with breast cancer.