Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, HER2 positive Breast Cancer
Brief 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.
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.
Interventions
DRUGT-DM1
antibody-drug conjugate of trastuzumab and emtansine
DRUGLapatinib
Dual tyrosine kinase inhibitor (HER2 and EGFR)
DRUGAbraxane
albumin-bound paclitaxel. Chemotherapy - microtubule inhibitor
Sponsors
The Methodist Hospital Research Institute
Jenny C. Chang, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed