T-DM1 and Non-pegylated Liposomal Doxorubicin in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer — THELMA  

Breast Cancer Clinical Trial

Official title: Phase I Multicenter Clinical Trial Evaluating the Combination of Trastuzumab Emtansine (T-DM1) and Non-pegylated Liposomal Doxorubicin in HER2-positive Metastatic Breast Cancer

Status Completed

Clinical Trial Summary

The primary goal is to determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy.

In addition, pharmacokinetic data on the combination of T-DM1 and liposomal doxorubicin will be obtained.

Clinical Trial Description

Subjects: Age ≥ 18 years with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer that have relapsed or progressed on or after taxanes and trastuzumab-based therapy. Subjects must have histologic or cytologic confirmation of the HER2-positive metastatic breast cancer. Evidence of measurable or evaluable metastatic disease is required.

Primary objective:

• To determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy.

Secondary objectives:

• To determine the efficacy of the combination of T-DM1 and non-pegylated liposomal doxorubicin, defined by the overall response rate (ORR), clinical benefit rate (CBR), number of progressions and number and reasons for deaths.

• To assess the safety profile of the combination of T-DM1 and non-pegylated liposomal doxorubicin, defined by all toxicities reported during the study.

• To evaluate the cardiac safety of the combination of T-DM1 and non-pegylated liposomal doxorubicin measured by left ventricular ejection fraction (LVEF) as assessed by echocardiography, cardiac troponin I and B-type natriuretic peptide (BNP) levels.

• To evaluate the potential role of single nucleotide polymorphisms (SNP) in the predisposition for developing cardiotoxicity.

• To analyze the pharmacokinetics (PK) profile of T-DM1 and its metabolites and non-pegylated liposomal doxorubicin.

Type of study: This is a prospective dose-finding, multicenter and open-label phase I clinical trial.

Treatment: Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and three cohorts of patients with three different dose levels of conventional non-pegylated liposomal doxorubicin (45 mg/m2, 50 mg/m2 and 60 mg/m2) IV on Day 1 in cycles of 21 days each are planned. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT02562378
• Study type: Interventional
• Source: MedSIR
• Status: Completed
• Phase: Phase 1
• Start date: October 2015
• Completion date: December 2018