Neratinib for Resistant or Recurrent Cancer

Recruiting at 8 trial locations

Overseen By Sameer Farouk Sait

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressive therapy

Disqualifiers: Uncontrolled infection, Cardiac disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

14 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of neratinib at different dose levels and to find out what effects, good and bad, it has on the patients and the cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had systemic chemotherapy or biologic therapy within 2 weeks or 5 half-lives of the agent used, whichever is shorter, before starting neratinib.

What data supports the effectiveness of the drug Neratinib for resistant or recurrent cancer?

Neratinib has shown promising results in reducing the risk of cancer recurrence in patients with early-stage HER2-positive breast cancer, especially when used soon after completing previous treatments. It has also demonstrated antitumor activity in HER2-positive breast cancer and other solid tumors. ^{1 2 3 4 5}

What is the safety profile of Neratinib in humans?

Neratinib is generally safe for humans, but it commonly causes diarrhea, which can be severe in some cases. Other side effects include nausea, abdominal pain, fatigue, vomiting, rash, and muscle spasms, but these are usually manageable with standard medical care. ^{1 2 3 6 7}

Research Team

Tanya Trippett, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for children and young adults aged 3 to 21 with recurrent or resistant cancers like brain tumors, lymphoma, leukemia, and solid tumors. They must have tried at least one treatment before, be able to swallow tablets or use a feeding tube, and have no severe heart issues. Females of childbearing age and males must agree to effective contraception.

Inclusion Criteria

I can swallow pills or have a feeding tube.

Women who could become pregnant must have a negative pregnancy test within 7 days before starting neratinib therapy.

I have been diagnosed with a solid tumor or lymphoma.

Exclusion Criteria

Pregnant or breast-feeding women

I am not being treated for another cancer, except for skin cancer or early-stage cervical cancer.

I have not had chemotherapy, biologic therapy, or radiation recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase I)

Neratinib is tested in groups of 3-6 patients to establish the maximum tolerated dose (MTD)

Variable, until MTD is established

Treatment (Phase II)

Determine whether the MTD shows a response to the tumor

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Neratinib

Trial Overview The study is testing the safety of different doses of Neratinib on young patients with cancer that has returned or didn't respond to previous treatments. It aims to discover both positive and negative effects this drug may have on their condition.

Participant Groups

Group I: Neratinib Experimental Treatment 1 Intervention

There are 2 parts to this study: a Phase I part and a Phase II part. The Phase I portion is known as the dose escalation phase where neratinib will be tested in groups of 3-6 patients to establish the maximum tolerated dose (MTD). The phase II portion will determine whether the MTD shows a response to the tumor.

Neratinib is already approved in United States, European Union for the following indications:

Approved in United States as Nerlynx for:

• Extended adjuvant treatment of women with early-stage HER2-positive breast cancer

Approved in European Union as Nerlynx for:

• Extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Milton S. Hershey Medical Center

Collaborator

Trials

515

Recruited

2,873,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Arkansas Children's Hospital Research Institute

Collaborator

Trials

141

Recruited

5,025,000+

Alberta Children's Hospital

Collaborator

Trials

58

Recruited

44,700+

Phoenix Children's Hospital

Collaborator

Trials

78

Recruited

5,014,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Findings from Research

Neratinib is an oral, irreversible inhibitor targeting HER1, HER2, and HER4, specifically developed for treating HER2-positive breast cancer, and is approved in the USA for patients who have previously received trastuzumab-based therapy.

The drug is currently in various stages of clinical development for other cancers, including metastatic breast cancer and solid tumors like non-small cell lung cancer and glioblastoma, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neratinib: First Global Approval. Deeks, ED.[2019]

Neratinib significantly reduces the risk of invasive disease recurrence or death in women with early-stage HER2-positive breast cancer who have completed trastuzumab therapy, as shown in the ExteNET trial over 12 months, with benefits observed at both 2 and 5 years post-treatment.

Patients with hormone receptor-positive disease and those who start neratinib within 1 year of completing trastuzumab experience greater benefits, leading to its approval in the EU as an extended adjuvant therapy for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU. Dhillon, S.[2021]

Neratinib combined with paclitaxel showed a high overall response rate of 73% in patients with HER2-positive breast cancer, indicating its efficacy as a treatment option.

The combination therapy had manageable side effects, with common adverse events including diarrhea and peripheral sensory neuropathy, but no dose-limiting toxicities were observed during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Chow, LW., Xu, B., Gupta, S., et al.[2023]

Neratinib has been shown to improve 2-year invasive disease-free survival in early-stage HER2-positive breast cancer patients after trastuzumab treatment, particularly in HER2+/HR+ tumors, according to the phase III ExteNET trial.

In phase II trials, neratinib demonstrated efficacy as both a standalone treatment and in combination with other therapies for HER2-positive metastatic breast cancer, with manageable side effects like diarrhea through early prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations. Kourie, HR., Chaix, M., Gombos, A., et al.[2019]

Neratinib, a tyrosine kinase inhibitor, shows promising efficacy in treating HER2-positive breast cancer, with a higher response rate when used in combination with other therapies compared to monotherapy.

While neratinib is associated with a high incidence of adverse events, particularly diarrhea (83.9% of patients), these side effects are generally manageable, and the drug has been linked to improved survival outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials. Tao, Z., Li, SX., Shen, K., et al.[2021]

Neratinib was approved by the FDA for the extended treatment of early-stage HER2-positive breast cancer, showing a significant improvement in invasive disease-free survival (iDFS) with a 2-year rate of 94.2% compared to 91.9% for placebo in a study of 2,840 women.

While neratinib is effective, it is associated with a high incidence of diarrhea (40% grade 3 or 4), which is the most common reason for treatment discontinuation, though most adverse effects are manageable and reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer. Singh, H., Walker, AJ., Amiri-Kordestani, L., et al.[2019]

Neratinib is an oral pan HER inhibitor that irreversibly blocks the activity of HER2 and other related receptors, showing promise in improving outcomes for patients with HER2-amplified breast cancer, which affects 20% to 25% of cases.

Current clinical trials are evaluating neratinib's safety and efficacy across various cancer types, including breast cancer, with a focus on its use in different treatment settings such as metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neratinib, A Novel HER2-Targeted Tyrosine Kinase Inhibitor. Tiwari, SR., Mishra, P., Abraham, J.[2019]

References

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

Neratinib: First Global Approval. [2019]

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

Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations. [2019]

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

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials. [2021]

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

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer. [2019]

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

Neratinib, A Novel HER2-Targeted Tyrosine Kinase Inhibitor. [2019]