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

Sponsor

Jenny C. Chang, MD (Other)

Overall Status

Completed

CT.gov ID

NCT02073916

Collaborator

The Methodist Hospital Research Institute (Other)

Enrollment

Location

Arm

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: T-DM1 Drug: Lapatinib Drug: Abraxane	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

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: Trastuzumab Emtansine TE Kadcyla Drug: Lapatinib Dual tyrosine kinase inhibitor (HER2 and EGFR) Other Names: Tykerb Drug: Abraxane albumin-bound paclitaxel. Chemotherapy - microtubule inhibitor Other Names: nab-paclitaxel

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:

Trastuzumab Emtansine

Kadcyla

Drug: Lapatinib

Dual tyrosine kinase inhibitor (HER2 and EGFR)

Other Names:

Tykerb

Drug: Abraxane

albumin-bound paclitaxel. Chemotherapy - microtubule inhibitor

Other Names:

nab-paclitaxel

Outcome Measures

Primary Outcome Measures

Maximum Tolerable Dose [approximately 16 weeks]
Maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer.

Secondary Outcome Measures

Dose Limiting Toxicities [From date of randomization through study follow up (approximately 16 weeks)]
Describe the dose-limiting toxicity (DLT) associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.
Measure toxicities associated with treatment combination [From date of randomization through study follow up (approximately 16 weeks)]
Describe and measure other toxicities associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.
Anti-tumor activity through imaging [approximately 16 weeks from randomization]
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
Plasma pharmacokinetics and pharmacodynamic effect of treatment combination [Day 1 and 1,2,4,and 24hours]
Determine the plasma pharmacokinetics of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.