TDM1 With Abraxane and Lapatinib for Metastatic HER2 Positive Breast Cancer (STELA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by The Methodist Hospital System
Sponsor:
Information provided by (Responsible Party):
The Methodist Hospital System
ClinicalTrials.gov Identifier:
NCT02073916
First received: February 18, 2014
Last updated: February 25, 2014
Last verified: February 2014
  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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: TDM1
Drug: Lapatinib
Drug: Abraxane
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by The Methodist Hospital System:

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.


Secondary Outcome Measures:
  • Dose Limiting Toxicities [ Time Frame: From date of randomization through study follow up (approximately 16 weeks) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From date of randomization through study follow up (approximately 16 weeks) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: approximately 16 weeks from randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 and 1,2,4,and 24hours ] [ Designated as safety issue: No ]
    Determine the plasma pharmacokinetics of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane.


Estimated Enrollment: 18
Study Start Date: October 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDM1 with Lapatinib followed by Abraxane
TDM1 with Laptinib followed by Abraxane
Drug: TDM1
•Drug: abraxane Intravenous repeating dose weekly
Other Names:
  • Trastuzumab Emtansine
  • TDM-1
  • TE
  • Kadcyla
Drug: Lapatinib
Oral repeating dose daily
Other Name: Tykerb
Drug: Abraxane
Intravenous repeating dose weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02073916

Contacts
Contact: Houston Methodist Cancer Center 713-441-0629 ccresearch@houstonmethodist.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Cancer Center    713-441-0629    ccresearch@houstonmethodist.org   
Principal Investigator: Jenny CN Chang, MD         
Sub-Investigator: Angel A Rodriguez, MD         
Sub-Investigator: Tejal Patel, MD         
Sub-Investigator: Daniel Lehane, MD         
Sub-Investigator: Monisha Singh, MD         
Sub-Investigator: Jorge Darcourt, MD         
Sponsors and Collaborators
The Methodist Hospital System
Investigators
Principal Investigator: Jenny CN Chang, MD The Methodist Hospital System
  More Information

Additional Information:
No publications provided

Responsible Party: The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT02073916     History of Changes
Other Study ID Numbers: 0813-0139
Study First Received: February 18, 2014
Last Updated: February 25, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by The Methodist Hospital System:
Breast Cancer
HER2 positive Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Ado-trastuzumab emtansine
Lapatinib
Maytansine
Paclitaxel
Trastuzumab
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014