TDM1 With Abraxane and Lapatinib for Metastatic HER2 Positive Breast Cancer
Overview[ - collapse ][ - ]
| Purpose | This open-label, single-center study will assess the safety and tolerability of combining trastuzumab emtansine (T-DM1) to 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. Anticipated time on study treatment is up to 12 cycles for patients metastatic breast cancer, until disease progression or unacceptable toxicity occurs. The purpose of this study is to test the safety of Trastuzumab Emtansine in combination with Abraxane and Lapatinib at different dose levels. The investigators are proposing in this phase Ib study to assess the maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer. The investigators hypothesize that combining antibody-drug conjugate trastuzumab-emtansine and lapatinib together with Abraxane will improve clinical efficacy by affecting both PI3K and ERK1,2 MAPK pathways. |
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| Condition | Metastatic Breast Cancer |
| Intervention | Drug: TDM1 Drug: Lapatinib Drug: Abraxane |
| Phase | Phase 1 |
| Sponsor | The Methodist Hospital System |
| Responsible Party | The Methodist Hospital System |
| ClinicalTrials.gov Identifier | NCT02073916 |
| First Received | February 18, 2014 |
| Last Updated | February 25, 2014 |
| Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | February 18, 2014 |
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| Last Updated Date | February 25, 2014 |
| Start Date | October 2013 |
| Estimated Primary Completion Date | October 2015 |
| Current Primary Outcome Measures | Maximum Tolerable Dose [Time Frame: approximately 16 weeks] [Designated as safety issue: Yes]Maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer. |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | TDM1 With Abraxane and Lapatinib for Metastatic HER2 Positive Breast Cancer |
|---|---|
| Official Title | Phase Ib Trial of Trastuzumab Emtansine In Combination With Lapatinib Plus Abraxane In Metastatic Her 2 Neu Over-Expressed Breast Cancer Patients |
| Brief Summary | This open-label, single-center study will assess the safety and tolerability of combining trastuzumab emtansine (T-DM1) to 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. Anticipated time on study treatment is up to 12 cycles for patients metastatic breast cancer, until disease progression or unacceptable toxicity occurs. The purpose of this study is to test the safety of Trastuzumab Emtansine in combination with Abraxane and Lapatinib at different dose levels. The investigators are proposing in this phase Ib study to assess the maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer. The investigators hypothesize that combining antibody-drug conjugate trastuzumab-emtansine and lapatinib together with Abraxane will improve clinical efficacy by affecting both PI3K and ERK1,2 MAPK pathways. |
| Detailed Description | Not Provided |
| Study Type | Interventional |
| Study Phase | Phase 1 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Metastatic Breast Cancer |
| Intervention | Drug: TDM1 •Drug: abraxane Intravenous repeating dose weekly Other Names:
Oral repeating dose daily Other Names: TykerbDrug: Abraxane Intravenous repeating dose weekly |
| Study Arm (s) | Experimental: TDM1 with Lapatinib followed by Abraxane TDM1 with Laptinib followed by Abraxane |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 18 |
| Estimated Completion Date | October 2015 |
| Estimated Primary Completion Date | December 2014 |
| Eligibility Criteria | 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. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Houston Methodist Cancer Center 713-441-0629 ccresearch@houstonmethodist.org |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT02073916 |
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| Other Study ID Numbers | 0813-0139 |
| Has Data Monitoring Committee | No |
| Information Provided By | The Methodist Hospital System |
| Study Sponsor | The Methodist Hospital System |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Jenny CN Chang, MD Houston Methodist Hospital |
| Verification Date | February 2014 |
Locations[ + expand ][ + ]
| Houston Methodist Hospital | Houston, Texas, United States, 77030 Contact: Cancer Center | 713-441-0629 | ccresearch@houstonmethodist.orgPrincipal Investigator: Jenny CN Chang, MD Recruiting |
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