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

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase Ib trial studies the side effects and best dose of nilotinib in preventing paclitaxel-induced peripheral neuropathy in stage I-III breast cancer patients who are receiving paclitaxel therapy. Chemotherapy is the usual or standard treatment for breast cancer. It kills cancer cells and lowers the chance that the cancer will come back. Sometimes, this treatment can cause numbness and tingling, especially in the hands and feet. This is called chemotherapy-induced peripheral neuropathy. This study aims to test the safety and effectiveness, both good and bad, of taking nilotinib in preventing chemotherapy-induced peripheral neuropathy.

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.

How does the drug Nilotinib differ from other treatments for preventing chemotherapy-induced peripheral neuropathy in breast cancer?

Nilotinib is unique because it is primarily known as a treatment for chronic myeloid leukemia, and its use for preventing chemotherapy-induced peripheral neuropathy (nerve damage) in breast cancer is novel. Unlike standard treatments, which are limited, Nilotinib's mechanism as a tyrosine kinase inhibitor (a type of drug that blocks certain enzymes) may offer a new approach to managing this condition. ^{1 2 3 4 5}

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 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]

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]

Citations

1. Netherlands 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. [2022]

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

Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy. [2021]

3. United States 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. [2022]

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

Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. [2022]

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

Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis. [2020]