T-DM1 With Abraxane and Lapatinib for Metastatic HER2 Positive Breast Cancer

Metastatic Breast Cancer Clinical Trial

— STELA  

Official title:

Phase Ib Trial of Trastuzumab Emtansine In Combination With Lapatinib Plus Abraxane In Metastatic Her 2 Neu Over-Expressed Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02073916
• Other study ID #: Pro00009544
• Secondary ID: 0813-0139
• Status: Completed
• Phase: Phase 1
• Start date: October 2013
• Est. completion date: December 2018

Study information

• Verified date: April 2019
• Source: The Methodist Hospital System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, single-center Phase Ib study will assess the safety and tolerability of combining trastuzumab emtansine (T-DM1) with Lapatinib and Abraxane in patients with metastatic HER2-positive breast cancer.

Description:

This open-label, single-center Phase Ib study will assess the safety and tolerability of combining trastuzumab emtansine (T-DM1) with Lapatinib and Abraxane in patients with metastatic HER2-positive breast cancer. Patients will receive Abraxane on Day 1 of each 1-week cycle and T-DM1 on Day 1 of each 3-week cycle. Patients with take Lapatinib orally daily. Patients will receive the study treatment for 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented metastatic Her2 over-expressed breast cancer.

• Age = 18 years Patients must have received at least two prior therapies for their malignant disease.

• Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE)

• Adequate organ function (cardiac ejection fraction of = 45%),

• CBC not less than .75 of institutional lower limit.

• Patients must have adequate liver function: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis Bilirubin < 1.5 mg/dL

• Patients must have adequate renal function: creatinine <1.5 mg/dL is recommended; however, institutional norms are acceptable.

• Negative serum or urine ß-hCG pregnancy test at screening for patients of childbearing potential

• Fertile patients must use effective contraception (barrier method - condoms, diaphragm
• also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed). Contraception method must be used during treatment and for three months after completing treatment Signed informed consent form (ICF)

Exclusion Criteria:

• Any medical or psychiatric condition that would prevent informed consent or limit survival to less than 4 weeks.

• Absolute QT interval of >460 msec in the presence of potassium >4.0mEq/L and Magnesium >1.8mg/dl.

• Patient with HIV and post- transplant associated lymphoproliferative disorders.

• Patient with concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of Trastuzumab Emtansine, Lapatinib or Abraxane.

• Pregnant or lactating women.

• Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab Emtansine, lapatinib, abraxane, or their components.

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.

• Subjects with ulcerative colitis are also excluded.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• T-DM1
antibody-drug conjugate of trastuzumab and emtansine
• Lapatinib
Dual tyrosine kinase inhibitor (HER2 and EGFR)
• Abraxane
albumin-bound paclitaxel. Chemotherapy - microtubule inhibitor

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Jenny C. Chang, MD	The Methodist Hospital System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerable Dose	Maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer.	approximately 16 weeks
Secondary	Dose Limiting Toxicities	Describe the dose-limiting toxicity (DLT) associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.	From date of randomization through study follow up (approximately 16 weeks)
Secondary	Measure toxicities associated with treatment combination	Describe and measure other toxicities associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.	From date of randomization through study follow up (approximately 16 weeks)
Secondary	Anti-tumor activity through imaging	Document anti-tumor activity of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer as assessed by RECIST 1:1 criteria	approximately 16 weeks from randomization
Secondary	Plasma pharmacokinetics and pharmacodynamic effect of treatment combination	Determine the plasma pharmacokinetics of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane.	Day 1 and 1,2,4,and 24hours