NCT04158947

A Study of HER2+ Breast Cancer Patients With Active Brain Metastases Treated With Afatinib & T-DM1 vs. T-DM1 Alone

A Randomized Study of HER2+ Breast Cancer Patients With Active Refractory Brain Metastases Treated With Afatinib in Combination With T-DM1 vs. T-DM1 Alone

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Sponsor: xuexin he · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is being done for the following reasons: The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of Afatinib that can be given safely with T-DM1. The purpose of the second part of the study (Phase II) is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep breast cancer from getting worse for a period of time.

Detailed description

This is a prospective, randomized, 2-arm, multicenter study to compare the safety and efficiency of T-DM1 + Afatinib versus T-DM1 in HER2-positive breast cancer patients with active refractory brain metastases. This study will be divided into two phases. The purpose of Phase I is to find out the highest dose of Afatinib that can be given safely with T-DM1. 3 \~ 24 eligible subjects will be enrolled in the study. The purpose of Phase II is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep subjects from getting worse for a period of time. The estimated ORR is 17.9 percent in the control group, hypothesis Afatinib can improve the prognosis of subjects, so objective respond rate (ORR) of experimental group is increased by 30 percent, with alpha = 0.025 (unilateral), beta = 0.1. The ratio of the experimental group and control group is 1:1, assuming a 5 percent loss rate. As a result, calculating by PASS 11 software, approximately 106 subjects will be enrolled, with 53 cases in the experimental group, and 53 cases in the control group.

Conditions

• HER2-positive Breast Cancer
• Brain Metastases

Interventions

Type	Name	Description
DRUG	Afatinib	Dose-escalation Phase (Phase I) - Afatinib Dose-escalation will proceed on the basis of dose limiting toxicity (DLT) during Cycle 1 starting at 20 mg/day. Dose level 1: 20 mg/day; Dose level 2: 30 mg/day; Dose level 3: 40 mg/day; Dose level 4: 50 mg/day. Dose-evaluation Phase (Phase II) - Patients will receive the highest dose of Afatinib with T-DM1 found in Phase I as study therapy
DRUG	T-DM1	Dose-escalation Phase (Phase I) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days. Dose-evaluation Phase (Phase II) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days.

Timeline

• Start date: 2020-05-10
• Primary completion: 2023-12-31
• Completion: 2024-03-31
• First posted: 2019-11-12
• Last updated: 2020-05-12

Locations

4 sites across 1 country: China