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NCT02673398

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

Completed Phase 2 Results posted Last updated 18 June 2023
What this trial tests

Phase 2 trial testing Comprehensive Geriatric Assessment in HER2 Positive Breast Carcinoma in 25 participants. Completed in 22 September 2022.

Timeline
2 December 2016
Primary endpoint
12 March 2020
22 September 2022

Quick facts

Lead sponsorCity of Hope Medical Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment25
Start date2 December 2016
Primary completion12 March 2020
Estimated completion22 September 2022
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

City of Hope Medical Center

Who can join

60 and older, any sex, with HER2 Positive Breast Carcinoma or Stage IV Breast Cancer AJCC v6 and v7. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent of Participants With Grade 2 or Higher Toxicities Primary · On treatment, 28 days per cycle up to 1 year

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.

GroupValue95% CI
Treatment (Neratinib)8059 – 93
Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting Secondary · On treatment, 28 days per cycle up to 1 year

Will be graded according to the NCI 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.

Diarrhea
GroupValue95% CI
Treatment (Neratinib)5
Vomiting
GroupValue95% CI
Treatment (Neratinib)2
Abdominal pain
GroupValue95% CI
Treatment (Neratinib)2
Nausea
GroupValue95% CI
Treatment (Neratinib)1
Rate of Participants With a Dose Reduction Secondary · On treatment, up to 48 months

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.

GroupValue95% CI
Treatment (Neratinib)3618 – 57
Rate of Participants Requiring Hospitalizations Secondary · On treatment, up to 48 months

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for hospitalizations.

GroupValue95% CI
Treatment (Neratinib)165 – 36
Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Secondary · Participants are evaluated every 12 weeks, up to 48 months

Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Stable Disease (S

GroupValue95% CI
Treatment (Neratinib)1
Treatment (Neratinib)11
Treatment (Neratinib)12
Treatment (Neratinib)1
Median Progression-free Survival (PFS) in Months Secondary · From the date treatment begins until the first date on which recurrence, progression or death due to any cause, assessed up to 48 months

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for PFS. PFS will be estimated using the product limit method of Kaplan and Meier.

GroupValue95% CI
Treatment (Neratinib)2.62.56 – 5.26
Median Overall Survival (OS) Secondary · Time from start of treatment to death due to any cause, assessed up to 48 months

OS will be estimated using the product limit method of Kaplan and Meier.

GroupValue95% CI
Treatment (Neratinib)17.410.3 – NA
Cancer-specific Geriatric Assessment Score Secondary · At day 0 of treatment

The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxici

GroupValue95% CI
Treatment (Neratinib)0.340.19 – 0.59
Pharmacokinetics of Steady State Neratinib Concentration Transformed Using a Logarithm Base 2 Secondary · Day 0 to day 15

Least squares regression was used to assess the relationship between steady state neratinib concentration, transformed using a logarithm base 2 transformation, and age

GroupValue95% CI
Treatment (Neratinib)4.7± 1.09

Adverse events — posted to ClinicalTrials.gov

Time frame: Through study completion, an average of 18 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Neratinib)
Serious: 10/25 (40%)
Deaths: 16/25

Serious adverse events (15 terms)

ReactionSystemTreatment (Neratinib)
DeathGeneral disorders
Abdominal painGastrointestinal disorders
DiarrheaGastrointestinal disorders
Pericardial tampoCardiac disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
AppendicitisInfections and infestations
Weight lossInvestigations
DehydrationMetabolism and nutrition disorders
T7 mets with spinal cord compressionMusculoskeletal and connective tissue disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Hypoxemic respiratory failureRespiratory, thoracic and mediastinal disorders
PneumoniaRespiratory, thoracic and mediastinal disorders
Other adverse events (23 terms — click to expand)

ReactionSystemTreatment (Neratinib)
DiarrheaGastrointestinal disorders
Lymphocyte count decreasedBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
White blood cell count decreasedBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
AnorexiaGeneral disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
DehydrationGeneral disorders
Generalized muscle weaknessGeneral disorders
Weight lossGeneral disorders
Acute kidney injuryInvestigations
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Skin lacerationSkin and subcutaneous tissue disorders
Ejection fraction decreasedCardiac disorders
HypertensionCardiac disorders
SyncopeCardiac disorders
Neutrophil count decreasedBlood and lymphatic system disorders
Platelet count decreasedBlood and lymphatic system disorders
HypoalbuminemiaInvestigations

Most-reported serious reactions: Death, Abdominal pain, Diarrhea, Pericardial tampo, Nausea, Vomiting, Appendicitis, Weight loss.

Data from ClinicalTrials.gov NCT02673398 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Neratinib for HER2-positive breast cancer with an overlooked option.
    Guo L, Shao W, Zhou C, Yang H, et al · · 2023 · cited 33× · PMID 37803271 · DOI 10.1186/s10020-023-00736-0
  2. Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer.
    Gadag S, Sinha S, Nayak Y, Garg S, et al · · 2020 · cited 25× · PMID 32521684 · DOI 10.3390/pharmaceutics12060524
  3. Analysis of Gut Microbiome Using Explainable Machine Learning Predicts Risk of Diarrhea Associated With Tyrosine Kinase Inhibitor Neratinib: A Pilot Study.
    Wong CW, Yost SE, Lee JS, Gillece JD, et al · · 2021 · cited 22× · PMID 33796451 · DOI 10.3389/fonc.2021.604584
  4. Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib.
    Ulrich L, Okines AFC. · · 2021 · cited 13× · PMID 34079368 · DOI 10.2147/bctt.s268451
  5. Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer.
    Yuan Y, Lee JS, Yost SE, Stiller T, et al · · 2021 · cited 7× · PMID 33663941 · DOI 10.1016/j.jgo.2021.02.020
  6. Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis.
    Grimsrud MM, Forster M, Goeppert B, Hemmrich-Stanisak G, et al · · 2024 · cited 4× · PMID 38967597 · DOI 10.1097/hc9.0000000000000461

Verify or expand the search:

Other trials of Comprehensive Geriatric Assessment

Trials testing the same drug.

Other recruiting trials for HER2 Positive Breast Carcinoma

Currently open trials in the same condition.

Other City of Hope Medical Center trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing