Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 2

Conditions: HER2-positive Breast Cancer

Treatments: Drug: Neratinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05154396

NCC3075

Details and patient eligibility

About

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).

Full 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.

Enrollment: 60 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups, including a placebo group

Neratinib escalation 2 weeks（group A）

Experimental group

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.

Treatment:

Drug: Neratinib

Neratinib escalation 4 weeks（group B）

Experimental group

Description:

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.

Treatment:

Drug: Neratinib

Neratinib standard dose control （group C）

Placebo Comparator group

Description:

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.

Treatment:

Drug: Neratinib