Clinical Trials /

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

NCT02073916

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 0813-0139
  • NCT ID: NCT02073916

Trial Conditions

  • Metastatic Breast Cancer

Trial Interventions

DrugSynonymsArms
TDM1Trastuzumab EmtansineTDM-1TEKadcylaTDM1 with Lapatinib followed by Abraxane
LapatinibTykerbTDM1 with Lapatinib followed by Abraxane
AbraxaneTDM1 with Lapatinib followed by Abraxane

Trial 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 weeks for patients metastatic breast cancer, until disease progression or unacceptable toxicity occurs. Subjects may continue on treatment past 12 weeks if responding to study treatment.

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

Trial Arms

NameTypeDescriptionInterventions
TDM1 with Lapatinib followed by AbraxaneExperimentalTDM1 with Laptinib followed by Abraxane
  • TDM1
  • Lapatinib
  • Abraxane

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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerable Dose
Time Frame:approximately 16 weeks
Safety Issue:Yes
Description:Maximum tolerated dose (MTD) of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane in metastatic Her2 over-expressed breast cancer.

Secondary Outcome Measures

Measure:Dose Limiting Toxicities
Time Frame:From date of randomization through study follow up (approximately 16 weeks)
Safety Issue:Yes
Description:Describe the dose-limiting toxicity (DLT) associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.
Measure:Measure toxicities associated with treatment combination
Time Frame:From date of randomization through study follow up (approximately 16 weeks)
Safety Issue:Yes
Description:Describe and measure other toxicities associated with Trastuzumab Emtansine in combination with Lapatinib plus Abraxane as assessed by CTCAE v4.0.
Measure:Anti-tumor activity through imaging
Time Frame:approximately 16 weeks from randomization
Safety Issue:No
Description: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
Measure:Plasma pharmacokinetics and pharmacodynamic effect of treatment combination
Time Frame:Day 1 and 1,2,4,and 24hours
Safety Issue:No
Description:Determine the plasma pharmacokinetics of Trastuzumab Emtansine in combination with Lapatinib plus Abraxane.

Trial Keywords

  • Breast Cancer
  • HER2 positive Breast Cancer