Kadcyla + Neratinib for Breast Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University Health Network, Toronto
Must be taking: T-DM1
Must not be taking: HER2 inhibitors
Disqualifiers: Metastatic disease, Cardiovascular diseases, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is for patients with early-stage HER2+ breast cancer who still have small amounts of cancer after initial treatments. They will take a drug called neratinib along with their usual treatment. Neratinib works by blocking signals that help cancer cells grow. The study aims to see if this combination improves patient outcomes.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must not have taken neratinib or other HER2 tyrosine kinase inhibitors before, and there is a 14-day period without radiation therapy required before starting the trial.
What data supports the effectiveness of the drug Neratinib (Nerlynx) for breast cancer?
Neratinib has been shown to significantly reduce the risk of breast cancer returning in patients with early-stage HER2-positive breast cancer, especially when started within a year of completing previous treatment. It has also demonstrated benefits in patients with advanced HER2-positive breast cancer when used in combination with other drugs.
12345Is the combination of Kadcyla and Neratinib safe for humans?
Neratinib, also known as Nerlynx, has been shown to have an acceptable safety profile in patients with HER2-positive breast cancer and other solid tumors. The most common side effect is diarrhea, which can be managed with medication and dose adjustments. Other side effects include nausea, abdominal pain, fatigue, and rash, but these are generally manageable and reversible.
45678How does the drug Kadcyla + Neratinib differ from other breast cancer treatments?
Kadcyla + Neratinib is unique because it combines two drugs: Kadcyla, which delivers chemotherapy directly to cancer cells, and Neratinib, an oral drug that blocks specific proteins (HER1, HER2, and HER4) involved in cancer growth. This combination targets HER2-positive breast cancer more effectively by using different mechanisms to attack the cancer cells.
4591011Eligibility Criteria
This trial is for adults over 18 with HER2+ stage I-III breast cancer, who've had surgery and are on T-DM1 therapy but still show signs of cancer at a molecular level. They should be in good health otherwise, able to follow the study plan, and willing to use effective birth control.Inclusion Criteria
I am over 18, had breast cancer surgery, and still have cancer after treatment with trastuzumab.
I am willing and able to follow the study's treatment plan and attend all visits.
I have no known allergies or adverse reactions to T-DM1 or neratinib.
+11 more
Exclusion Criteria
My cancer has spread to other parts of my body.
I have HIV that is not being treated with medication.
I have or had hepatitis B or C, but it's not active now.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive standard T-DM1 adjuvant therapy with Neratinib for up to 12 months
12 months
Every 3 weeks for T-DM1 infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Participant Groups
The trial tests if adding neratinib (a pill taken daily) to standard T-DM1 therapy can clear remaining cancer traces after initial treatment. It's given for up to a year unless there's recurrence or side effects leading to stopping the drug.
1Treatment groups
Experimental Treatment
Group I: Neratinib ArmExperimental Treatment1 Intervention
Standard T-DM1 (3.6mg/kg) IV infusion every 3 weeks administered with Neratinib (160 mg) orally once daily up to 1 year.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Health Network: Princess Margaret Cancer CentreToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
References
Neratinib in advanced HER2-positive breast cancer: experience from the royal Marsden hospital. [2022]To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer in a real-world setting.
Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2‑positive breast cancer: an NSABP Foundation Research Program phase I study. [2019]Neratinib is an oral, small-molecule inhibitor that irreversibly binds to pan-HER (ErbB) receptor tyrosine kinases. Studies suggest that dual anti-HER therapies utilized in breast cancer patients are more efficacious than single agents in both the metastatic and neoadjuvant settings. In this phase I study, neratinib was combined with trastuzumab and paclitaxel in metastatic HER2-positive patients.
Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer. [2023]Label="PURPOSE">Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS.
Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU. [2021]Neratinib (Nerlynx®) is an oral, irreversible pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor of HER1, HER2 and HER4. Neratinib therapy for 12 months significantly reduced the risk of invasive disease recurrence or death relative to placebo at both 2 and 5 years post-randomization in the pivotal ExteNET trial in women with early-stage HER2-positive breast cancer who had completed adjuvant trastuzumab. Subgroup analyses showed that patients with hormone receptor (HRc)-positive disease derived greater benefit with neratinib than patients with HRc-negative disease, and patients who initiated neratinib within 1 year of completing trastuzumab had better outcomes than those who started treatment 1-2 years after trastuzumab. This led to the approval of neratinib in the EU as extended adjuvant therapy for patients with early-stage HRc-positive, HER2-positive breast cancer and who are less than 1 year from completion of prior adjuvant trastuzumab-based therapy. It is the first agent of its class to be approved in the EU in this setting. As with other tyrosine kinase inhibitors, diarrhoea, which was manageable with antidiarrhoeal prophylaxis and/or dose modifications, was the most common any-grade or grade ≥ 3 treatment-emergent adverse event with neratinib. Thus, current evidence indicates that neratinib provides a valuable option to reduce the risk of recurrence in this setting and has been included in the updated ESMO patient guide as an extended adjuvant therapy for some patients.
Neratinib: First Global Approval. [2019]Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.
Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. [2023]Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours.
U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer. [2019]On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified HR of 0.66 [95% confidence interval (CI), 0.49-0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%-95.4%) in patients treated with neratinib versus 91.9% (95% CI, 90.2%-93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Clin Cancer Res; 24(15); 3486-91. ©2018 AACRSee related commentary by Unni et al., p. 3483.
Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials. [2021]Neratinib is a novel pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor that has shown promising activity against several types of malignancies, especially HER2-overexpressing breast cancer.
Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study. [2022]Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors.
Combining Neratinib with CDK4/6, mTOR, and MEK Inhibitors in Models of HER2-positive Cancer. [2022]Label="PURPOSE">Neratinib is an irreversible, pan-HER tyrosine kinase inhibitor that is FDA approved for HER2-overexpressing/amplified (HER2+) breast cancer. In this preclinical study, we explored the efficacy of neratinib in combination with inhibitors of downstream signaling in HER2+ cancers in vitro and in vivo.
Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. [2020]Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer.