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

NCT04366713 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PUMA-NER-62032019-001896-35
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HER2 Amplified Breast Cancer

Keywords

HER2-Positive; Breast Cancer; Colon Pathology; Colonoscopy

Outcome Measures

Primary Outcomes (1)

• Changes in Colon Pathology

  The primary endpoint is to describe the changes in colon pathology between the baseline colonoscopy and the second colonoscopy.

  From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.

Secondary Outcomes (1)

• Incidence and Severity of Diarrhea

  From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.

Study Arms (1)

Neratinib

EXPERIMENTAL

Neratinib with loperamide prophylaxis, and capecitabine for participants treated for metastatic breast cancer

Drug: Neratinib; Drug: Capecitabine; Drug: Loperamide

Interventions

Neratinib DRUG

Administered orally once daily as a single daily dose of 240 mg

Also known as: Nerlynx

Neratinib

Capecitabine DRUG

Administered orally twice daily at 750 mg/m\^2 for 14 days of each 21 day treatment cycle

Neratinib

Loperamide DRUG

Administered orally for prophylaxis for 28 days and then as needed

Neratinib

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years.
• Histologically confirmed stage 1 through stage 4 primary adenocarcinoma of the breast.
• Documented HER2 overexpression or gene-amplified tumor by a validated approved method.
• 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.
• Participants with mBC must have had at least 2 prior HER2-directed regimens.
• Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
• Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.
• 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. \[Women are considered postmenopausal if they are ≥12 months without menses, in the absence of endocrine or anti-endocrine therapies.\]
• 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.
• Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events related to prior therapies (excluding alopecia, neuropathy, and nail changes).
• No major bleeding diathesis or use of anticoagulants that would pose a high risk for endoscopic procedure.
• Provide written, informed consent to participate in the study and follow the study procedures.

You may not qualify if:

• Participants with confirmed stage 1 to stage 3c currently receiving chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer.
• Participants with mBC who have received prior capecitabine or HER2 directed tyrosine kinase inhibitor (TKI) therapy.
• 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).
• 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.
• 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.
• Corrected QT Interval (QTc) interval \>0.450 seconds (males) or \>0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP).
• Diagnosis of inflammatory bowel disease
• Screening laboratory assessments outside the following limits:
• Active, unresolved infections.
• 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.
• Currently pregnant or breast-feeding.
• 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).
• Clinically active infection with hepatitis B or hepatitis C virus.
• 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.
• Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (1)

Hospital CUF Descobertas

Lisbon, 1998-018, Portugal

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

neratinib; Capecitabine; Loperamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Piperidines

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology, Inc.

clinicaltrials@pumabiotechnology.com

1-424-248-6500

Study Officials

• Chief Scientific Officer

  Puma Biotechnology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: April 29, 2020
• Study Start: June 30, 2020
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: February 10, 2023
• Results First Posted: February 10, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.
• Access Criteria: Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest. Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.

Locations

PT (1)