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Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

Primary Purpose

HER2-positive Breast Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Neratinib

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Neratinib escalation 2 weeks（group A）

Neratinib escalation 4 weeks（group B）

Neratinib standard dose control （group C）

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Secondary Endpoint

3-year invasive disease-free survival (iDFS%) and other safety events

Full Information

NCT ID

NCT05154396

First Posted

October 9, 2021

Last Updated

November 29, 2021

Sponsor

Chinese Academy of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT05154396

Brief Title

Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

Official Title

Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2022 (Anticipated)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese Academy of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neratinib escalation 2 weeks（group A）

Arm Type

Experimental

Arm Description

Arm Title

Neratinib escalation 4 weeks（group B）

Arm Type

Experimental

Arm Description

Arm Title

Neratinib standard dose control （group C）

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Neratinib

Other Intervention Name(s)

Loperamide prophylaxis

Intervention Description

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

Primary Outcome Measure Information:

Title

Primary Endpoint

Description

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

Time Frame

up to 3 year after the last patient enrolled

Secondary Outcome Measure Information:

Title

Secondary Endpoint

Description

3-year invasive disease-free survival (iDFS%) and other safety events

Time Frame

up to 3 year after the last patient enrolled

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Peng Yuan

Phone

01087787245

yuanpengyp01@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Xue Wang

Phone

01087787242

wxyxyuki@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peng Yuan

Organizational Affiliation

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

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