Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

This is a prospective study on the prevention of Neratinib-related diarrhea in a Chinese population, exploring the best options for reducing the incidence of neratinib-related diarrhea through either pharmacologic intervention (prophylactic antidiarrheal therapy) or non-pharmacologic intervention (dose escalation program).

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Neratinib

Detailed Description

This is A prospective, randomized, single-center clinical trial, divided into 3 groups (experimental group: group A and group B, control group: group C), planned sixty patients were enrolled, with 20 patients in each group.

Experimental group: Group A (n=20) and group B (n=20) were given neratinib dose escalation regimen foranti-HER2 adjuvant therapy.In group A, the dose of neratinib climbed up to 240mg within 2 weeks, and in group B, the dose climbed up to 240mg within 4 weeks.

Control group: Group C (n=20) was given 240mg neratinib initially, but prophylactic loperamide antidiarrhea treatment was given at the same time within 2 months.

Diarrhea caused by neratinib often occurred within 1-2 months of initial treatment, so small dose of neratinib was used in both group A and group B at the time of initial treatment.

The incidence and severity of neratinib-related diarrhea in the three groups were observed, and DFS and other neratinib-related adverse events were followed up for a long time. The study is to evaluate the safety and efficacy of neratinib dose escalation regimen and conventional dose combined with loperamide regimen in enhanced anti-HER2 adjuvant therapy for early HER2-positive breast cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Yuan; Phone Number: 01087787245; Email: yuanpengyp01@163.com
• Study Contact Backup: Name: Xue Wang; Phone Number: 01087787242; Email: wxyxyuki@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age between 18 and 75 year-old women；
• ECOG score: 0-1；
• HER2 positive breast cancer diagnosed histologically is defined as HER2 (3+) by immunohistochemistry or HER2 (2+) with positive FISH test；
• Postoperative pathological stage ⅱ → ⅲ, or initial stage (before neoadjuvant therapy) ⅱ → ⅲ, radiographic assessment showed no metastasis;
• Complete 1 year of anti-HER2 therapy with trastuzumab, prior use of pertuzumab neoadjuvant + adjuvant therapy or T-DM1 adjuvant therapy is permitted;
• No major organ dysfunction, contraception;
• The patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the Informed Consent Form.

Exclusion Criteria:

• Patients who are allergic to the study drug, cannot take the drug orally, or refuse the medication regimen;
• Prior treatment with TKI anti-HER-2 drugs (e.g. Lapatinib, Pyrotinib, etc.);
• Patients were enrolled in other studies or stopped taking other drugs within 4 weeks;
• Patients with serious dysfunction of important organs (heart, liver and kidney);
• Patients with other malignancies, other than cured non-melanoma skin cancer, carcinoma in situ of the cervix and other tumors that have been cured for at least 5 years;
• In pregnancy, lactation patients;
• In the active stage of other acute or chronic infectious diseases;
• The patients have uncontrollable mental illness;
• There is a known history of human immunodeficiency virus;
• There are other circumstances in which the investigator suggested that the patient should not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neratinib escalation 2 weeks（group A）; Neratinib: 120mg/ day for days 1-7, 160mg/ day for days 8-14, and then 240mg/ day to complete 1-year treatment, or to tumor recurrence and metastasis, new breast cancer, or unacceptable adverse reactions within 1 year.	Drug: Neratinib; Patients with her2-positive early breast cancer were treated with a dose escalation regimen of neratinib or a routine dose of neratinib combined with loperamide; Other Names: Loperamide prophylaxis
EXPERIMENTAL: Neratinib escalation 4 weeks（group B）; Neratinib: 160mg/ day for days 1-14, 200mg/ day for days 15-28, and then 240mg/ day for 1 year, or to tumor recurrence and metastasis, new breast cancer, or unacceptable adverse reactions within 1 year.	Drug: Neratinib; Patients with her2-positive early breast cancer were treated with a dose escalation regimen of neratinib or a routine dose of neratinib combined with loperamide; Other Names: Loperamide prophylaxis
PLACEBO_COMPARATOR: Neratinib standard dose control （group C）; Neratinib: 240mg/ day for 1 year, or to tumor recurrence and metastasis, new breast cancer or unacceptable adverse reactions within 1 year. Loperamide prophylaxis: 4mg three times daily on days 1-14 and 4mg twice daily on days 15-56, followed by as needed, not exceeding 16mg/ day.	Drug: Neratinib; Patients with her2-positive early breast cancer were treated with a dose escalation regimen of neratinib or a routine dose of neratinib combined with loperamide; Other Names: Loperamide prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint	Incidence of grade ≥3 diarrhea in patients with her2-positive early breast cancer treated with neratinib dose escalation versus neratinib conventional dose combined with loperamide	up to 3 year after the last patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint	3-year invasive disease-free survival (iDFS%) and other safety events	up to 3 year after the last patient enrolled

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: October 9, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (ACTUAL): December 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): December 13, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Gastrointestinal Agents; Antidiarrheals; Loperamide
• Other Study ID Numbers: NCC3075

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No