Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer

NCT02673398 | Completed Phase 2 Results DMC

• 4 other identifiers: 15342NCI-2015-02282K12CA001727P30CA033572
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

Brief Summary

This phase II trial studies the side effects of and how well neratinib works in treating older patients with stage IV HER2-positive breast cancer. Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

HER2 Positive Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Grade 2 or Higher Toxicities

  Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tables will be created to summarize the toxicities and side effects by organ system, attribution and severity for all participants that receive at least one dose of neratinib. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to neratinib.

  On treatment, 28 days per cycle up to 1 year

Secondary Outcomes (8)

• Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting

  On treatment, 28 days per cycle up to 1 year

• Rate of Participants With a Dose Reduction

  On treatment, up to 48 months

• Rate of Participants Requiring Hospitalizations

  On treatment, up to 48 months

• Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST)

  Participants are evaluated every 12 weeks, up to 48 months

• Median Progression-free Survival (PFS) in Months

  From the date treatment begins until the first date on which recurrence, progression or death due to any cause, assessed up to 48 months

Study Arms (1)

Treatment (neratinib)

EXPERIMENTAL

Patients receive neratinib 240mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Comprehensive Geriatric Assessment; Other: Laboratory Biomarker Analysis; Drug: Neratinib; Other: Pharmacological Study

Interventions

Comprehensive Geriatric Assessment OTHER

Ancillary studies

Treatment (neratinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (neratinib)

Neratinib DRUG

Given PO

Also known as: (2E)-N-(4-((3-chloro-4-((pyridin-2-yl)methoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide, HKI 272, HKI-272, PB 272, PB-272

Treatment (neratinib)

Pharmacological Study OTHER

Correlative studies

Treatment (neratinib)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance 0-2
• Life expectancy of greater than 12 weeks
• Histologically or cytologically proven metastatic breast cancer (metastases can be proven with imaging results in certain circumstances provided that the initial tumor was demonstrated histologically)
• Stage IV HER2/Neu positive breast cancer patients who failed previous anti-HER2 targeted therapies
• HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but activating somatic mutations of HER2 gene identified through genomic sequencing including but not limited to the following (Clinical Laboratory Improvement Act \[CLIA\] certified lab test): missense substitutions (G309A, G309E, S310F, S310Y, S653C, V659E, R678Q, V697L, T733I, L755S, L755P, E757A, D769H, D769Y, D769N, G776V, G776C, V777L, L841V, V842I, R849W, L869R, R896C); insertions/deletions (A775\_G776insYVMA aka Y772\_A755dup, G776VinsC, G776AinsVGC, G776 insertions, G778\_S779insCPG, P780\_781insGSP aka G778\_P780dup, L755\_T759del) and/or HER3 activating mutations; there is no limitation on the number of prior lines of systemic therapy or HER2-targeted therapies (prior neratinib not allowed)
• Both measurable as well as non-measurable disease will be allowed
• Hemoglobin \>= 9 g/dL (after transfusion, if necessary) within 4 weeks of pre-registration
• Total bilirubin within normal institutional limits within 4 weeks of pre-registration
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal within 4 weeks of pre-registration
• Creatinine clearance \>= 30 mL/min as calculated by Cockcroft-Gault formula within 4 weeks of pre-registration
• Baseline left ventricular ejection fraction LVEF \>= 50% as evaluated by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• All grade \>= 2 toxicities other than alopecia from prior therapy have resolved by the time of study commencement
• Patient must have completed radiation therapy with adequate recovery of bone marrow and organ functions, before starting neratinib
• Patient with stable or treated brain metastases are eligible; asymptomatic patients with metastatic brain disease who have been on a stable dose of corticosteroids for treatment of brain metastases for at least 14 days are eligible to participate in the study

You may not qualify if:

• Prior treatment with neratinib
• Concurrent usage of other investigational agents, chemotherapy, or hormone therapy; prior chemotherapy, hormonal therapy, targeted therapy, and investigational agents are allowed but all toxicities grade \>= 2 must have resolved by the time of study commencement (except alopecia)
• Any major surgery =\< 28 days prior to the initiation of investigational products
• Received chemotherapy or biologic therapy =\< 3 weeks prior to the start of neratinib
• Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of \>= 2, including individuals who currently use digitalis specifically for congestive heart failure), unstable angina, myocardial infarction within 12 month of enrollment or ventricular arrhythmia
• Concurrent use of digoxin due to cardiac disease; corrected QT (QTc) interval \>= 450 milliseconds in men and \>= 470 milliseconds in women within 2 weeks of registration or known history of QTc prolongation or Torsades de Pointes
• Inability to take oral medication
• Other malignancy within the past 3 years with the exception of: a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) cervix or vulva carcinoma in situ; c) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn?s disease, malabsorption, or grade \>= 2 National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v.4.0 diarrhea of any etiology at baseline)
• Known clinically active infection with hepatitis B or hepatitis C virus
• Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situations that would, in the investigator?s judgment, makes the patient inappropriate for this study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

City of Hope Corona

Corona, California, 92879, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

City of Hope Mission Hills

Mission Hills, California, 91345, United States

Location

City of Hope Rancho Cucamonga

Rancho Cucamonga, California, 91730, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope West Covina

West Covina, California, 91790, United States

Location

Related Publications (2)

• Wong CW, Yost SE, Lee JS, Gillece JD, Folkerts M, Reining L, Highlander SK, Eftekhari Z, Mortimer J, Yuan Y. Analysis of Gut Microbiome Using Explainable Machine Learning Predicts Risk of Diarrhea Associated With Tyrosine Kinase Inhibitor Neratinib: A Pilot Study. Front Oncol. 2021 Mar 10;11:604584. doi: 10.3389/fonc.2021.604584. eCollection 2021.

  PMID: 33796451 DERIVED

• Yuan Y, Lee JS, Yost SE, Stiller T, Blanchard MS, Padam S, Katheria V, Kim H, Sun C, Tang A, Martinez N, Patel ND, Sedrak MS, Waisman J, Li D, Sanani S, Presant CA, Mortimer J. Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer. J Geriatr Oncol. 2021 Jun;12(5):752-758. doi: 10.1016/j.jgo.2021.02.020. Epub 2021 Mar 2.

  PMID: 33663941 DERIVED

MeSH Terms

Interventions

Geriatric Assessment; neratinib

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Status; Demography; Population Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Results Point of Contact

• Title: Dr. Yuan Yuan
• Organization: City of Hope

Yuyuan@coh.org

626-359-8111

Study Officials

• Mina Sedrak, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 3, 2016
• Study Start: December 2, 2016
• Primary Completion: March 12, 2020
• Study Completion: September 22, 2022
• Last Updated: June 18, 2023
• Results First Posted: March 16, 2022

Record last verified: 2023-06

Locations

US (7)