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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: T-DM1; Drug: Lapatinib; Drug: Abraxane

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 β-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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-DM1 + Lapatinib + Abraxane; T-DM1 with Laptinib followed by Abraxane	Drug: T-DM1; antibody-drug conjugate of trastuzumab and emtansine; Other Names: Kadcyla; TE; Trastuzumab Emtansine; Drug: Lapatinib; Dual tyrosine kinase inhibitor (HER2 and EGFR); Other Names: Tykerb; Drug: Abraxane; albumin-bound paclitaxel. Chemotherapy - microtubule inhibitor; Other Names: nab-paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
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

Collaborators and Investigators

• Sponsor: Jenny C. Chang, MD
• Collaborators: The Methodist Hospital Research Institute
• Investigators: Principal Investigator: Jenny C Chang, MD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: February 18, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 27, 2014

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2 positive Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel; Ado-Trastuzumab Emtansine; Lapatinib
• Other Study ID Numbers: Pro00009544; 0813-0139 (Other Identifier: HMRI IRB)