NCT02562378

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

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab and non-pegylated liposomal doxorubicin	3 Cohorts (3+3 design): Cohort 1- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (45 mg/m2) IV Cohort 2- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (50 mg/m2) IV Cohort 3- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV

Timeline

• Start date: 2015-10-01
• Primary completion: 2018-12-01
• Completion: 2018-12-01
• First posted: 2015-09-29
• Last updated: 2022-02-23
• Results posted: 2022-01-18

Locations

4 sites across 2 countries: France, Spain