Clinical Trials /

A Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib

NCT04366713

Description:

This study will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib. Colonoscopy will be performed after eligibility has been confirmed, prior to administration of the first dose of neratinib, and after 28 days of neratinib treatment.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
  • Official Title: An Open-Label Phase 2 Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib

Clinical Trial IDs

  • ORG STUDY ID: PUMA-NER-6203
  • SECONDARY ID: 2019-001896-35
  • NCT ID: NCT04366713

Conditions

  • HER2 Amplified Breast Cancer

Interventions

DrugSynonymsArms
NeratinibNerlynxNeratinib
CapecitabineNeratinib
LoperamideNeratinib

Purpose

This study will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib. Colonoscopy will be performed after eligibility has been confirmed, prior to administration of the first dose of neratinib, and after 28 days of neratinib treatment.

Detailed Description

      This is an open-label, phase 2 study that will investigate colon pathology in patients with
      HER2-positive breast cancer treated with neratinib as monotherapy.

      All patients will receive neratinib for the first 28 days as a single daily dose of 240 mg.

      Colonoscopy will be performed after eligibility has been confirmed, but prior to
      administration of the first dose of neratinib and at Day 30 (± 3 days) the conclusion of
      Cycle 1 (28 days).

      Following the second study colonoscopy procedure:

        -  For patients being treated for stage 1 to 3c breast cancer in the extended adjuvant
           setting, neratinib will continue to be administered at a single daily dose of 240 mg
           until completion of one year of therapy from start of treatment, or until disease
           recurrence (as determined by the Investigator), death, unacceptable toxicity, or other
           specified withdrawal criterion.

        -  For patients being treated for metastatic breast cancer (mBC), capecitabine will be
           introduced after the second study colonoscopy procedure at a dose of 750mg/m2 twice
           daily for 14 days of each 21 day treatment cycle, with neratinib administered
           continuously throughout at 240 mg daily, until disease progression, death, unacceptable
           toxicity, or other specified withdrawal criterion.

      All patients will receive loperamide diarrhea prophylaxis daily for one 28-day cycle and then
      as needed.
    

Trial Arms

NameTypeDescriptionInterventions
NeratinibExperimentalNeratinib with loperamide prophylaxis, and capecitabine for participants treated for metastatic breast cancer
  • Neratinib
  • Capecitabine
  • Loperamide

Eligibility Criteria

        INCLUSION CRITERIA

          1. Aged ≥18 years.

          2. Histologically confirmed stage 1 through stage 4 primary adenocarcinoma of the breast.

          3. Documented HER2 overexpression or gene-amplified tumor by a validated approved method.

          4. Participants with confirmed stage 1 to stage 3c breast cancer receiving extended
             adjuvant treatment with neratinib monotherapy must have completed a course of prior
             adjuvant trastuzumab or experienced side effects that resulted in early
             discontinuation of trastuzumab that have since resolved.

          5. Participants with mBC must have had at least 2 prior HER2-directed regimens.

          6. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition
             scan (MUGA) or echocardiogram (ECHO).

          7. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.

          8. Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women
             of reproductive capacity (those who are biologically capable of having children) and
             for women less than 12 months after menopause. [Women are considered postmenopausal if
             they are ≥12 months without menses, in the absence of endocrine or anti-endocrine
             therapies.]

          9. Women of childbearing potential must agree and commit to the use of a highly effective
             non-hormonal method of contraception, i.e., intrauterine device, bilateral tubal
             ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle
             of the participant), from the time of informed consent until 28 days after the last
             dose of the investigational products. Men (male participant) with a female partner of
             childbearing potential must agree and commit to use condom and the female partner must
             agree and commit to use a highly effective method of contraception (i.e., any of the
             above methods, or for females, hormonal contraception associated with inhibition of
             ovulation) while on treatment and for 3 months after last dose of investigational
             products.

         10. Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events
             related to prior therapies (excluding alopecia, neuropathy, and nail changes).

         11. No major bleeding diathesis or use of anticoagulants that would pose a high risk for
             endoscopic procedure.

         12. Provide written, informed consent to participate in the study and follow the study
             procedures.

        EXCLUSION CRITERIA:

          1. Participants with confirmed stage 1 to stage 3c currently receiving chemotherapy,
             radiation therapy, immunotherapy, or biotherapy for breast cancer.

          2. Participants with mBC who have received prior capecitabine or HER2 directed tyrosine
             kinase inhibitor (TKI) therapy.

          3. Currently using drugs that have been implicated as causing microscopic colitis/watery
             diarrhea, such as acarbose, aspirin, proton pump inhibitors, nonsteroidal
             anti-inflammatory drugs (NSAIDs), histamine H2 receptor antagonists, selective
             serotonin reuptake inhibitors, and ticlopidine (Pardi, 2017).

          4. Major surgery within <28 days of starting treatment or received chemotherapy,
             investigational agents, or other cancer therapy, except hormonal therapy (e.g.,
             tamoxifen, aromatase inhibitors), <14 days prior to the initiation of investigational
             products.

          5. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart
             failure (New York Heart Association functional classification of ≥2; including
             individuals who currently use digitalis, beta-blockers, or calcium channel blockers
             specifically for congestive heart failure), unstable angina, myocardial infarction
             within 12 months of enrollment, or ventricular arrhythmia.

          6. Corrected QT Interval (QTc) interval >0.450 seconds (males) or >0.470 (females), or
             known history of QTc prolongation or Torsade de Pointes (TdP).

          7. Diagnosis of inflammatory bowel disease

          8. Screening laboratory assessments outside the following limits:

             Laboratory Parameters Required Limit for Exclusion Absolute neutrophil count (ANC)
             <1,000/µl (<1.0 x 109/L) Platelet count <50,000/µl (<100 x 109/L) Hemoglobin <8 g/dL
             (transfusions allowed) Transfusions must be at least 14 days prior to initiation of
             treatment Total bilirubin >1.5 x institutional upper limit of normal (ULN) (in case of
             known Gilbert's syndrome, <2 x ULN is allowed) Aspartate aminotransferase (AST) and/or
             alanine aminotransferase (ALT) >2.5 x institutional ULN (>5 x ULN if liver metastases
             are present) Creatinine Creatinine clearance <30 mL/min (as calculated by
             Cockcroft-Gault formula A or Modification of Diet in Renal Disease formula B)
             International Normalized Ratio (INR) >1.5 a Cockcroft and Gault, 1976 b Levey et al,
             1999

          9. Active, unresolved infections.

         10. Participants with a second malignancy, other than adequately treated non-melanoma skin
             cancers, in situ melanoma or in situ cervical cancer. Participants with other
             non-mammary malignancies must have been disease free for at least 5 years.

         11. Currently pregnant or breast-feeding.

         12. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg,
             Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common
             Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any
             etiology at baseline).

         13. Clinically active infection with hepatitis B or hepatitis C virus.

         14. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric
             illness/social situations that could, in the Investigator's judgment, make the person
             inappropriate for this study.

         15. Known hypersensitivity to any component of the investigational products; known
             allergies to any of the medications or components of medications used in the trial.

         16. Unable or unwilling to swallow tablets
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes in Colon Pathology
Time Frame:From baseline to 28 days after neratinib treatment
Safety Issue:
Description:The primary endpoint is to describe the changes in colon pathology observed over the first 28 days of neratinib therapy. The clinical study report will be a descriptive summary of these changes using listings and narratives.

Secondary Outcome Measures

Measure:Incidence and Severity of Diarrhea
Time Frame:From baseline to 28 days after neratinib treatment
Safety Issue:
Description:Incidence and severity of diarrhea will be summarized according to the NCI-CTCAE version 4.0 in the first 28-day cycle of neratinib treatment.
Measure:Change in Erythrocyte Sedimentation Rate (ESR)
Time Frame:From the first baseline colonoscopy to the second colonoscopy, up to 33 days
Safety Issue:
Description:Change in the serological inflammatory marker erythrocyte sedimentation rate (ESR) will be assessed from baseline at the time of the first colonoscopy to the second colonoscopy. The unit of measurement is mm/hr.
Measure:Change in C-reactive protein (CRP)
Time Frame:From the first baseline colonoscopy to the second colonoscopy, up to 33 days
Safety Issue:
Description:Change in the serological inflammatory marker C-reactive protein (CRP) will be assessed from baseline at the time of the first colonoscopy to the second colonoscopy. The unit of measurement is mg/L.
Measure:Change in Fecal Calprotectin
Time Frame:From the first baseline colonoscopy to the second colonoscopy, up to 33 days
Safety Issue:
Description:Change in the stool inflammatory marker fecal calprotectin will be assessed from baseline at the time of the first colonoscopy to the second colonoscopy. The unit of measurement is mcg/g.
Measure:Change in Fecal Elastase
Time Frame:From the first baseline colonoscopy to the second colonoscopy, up to 33 days
Safety Issue:
Description:Change in the stool inflammatory marker fecal elastase will be assessed from baseline at the time of the first colonoscopy to the second colonoscopy. The unit of measurement is mcg/g.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Puma Biotechnology, Inc.

Trial Keywords

  • HER2-Positive
  • Breast Cancer
  • Colon Pathology
  • Colonoscopy

Last Updated

April 24, 2020