NCT02725541

Brief Summary

This is an open label, neoadjuvant phase II study to evaluate the objective response, toxicity, and safety of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Trastuzumab emtansine at a dose of 3.6 mg/kg will be intravenously administered every 3 weeks for a total of 6 weeks. Patients who achieve a partial or complete response after the 6-week treatment (responders) will continue on trastuzumab emtansine for an additional 12 weeks.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Mar 2016

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2016

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

March 18, 2016

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 1, 2016

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2019

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2019

Completed
Last Updated

September 14, 2016

Status Verified

September 1, 2016

Enrollment Period

3.1 years

First QC Date

March 18, 2016

Last Update Submit

September 12, 2016

Conditions

Breast Cancer

Keywords

HER2 equivocalTrastuzumab emtansineBreast cancer

Outcome Measures

Primary Outcomes (1)

  • Objective response rate

    Determine the objective response rate after 6 weeks of neoadjuvant trastuzumab emtansine (RECIST 1.1)

    6 weeks

Secondary Outcomes (2)

  • Radiological response

    6 weeks

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

    18 weeks

Other Outcomes (3)

  • Pathological complete response (pCR) rate

    18 weeks

  • pCR rate

    18 weeks

  • Correlative markers of trastuzumab emtansine response

    6 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

Trastuzumab emtansine at a dose of 3.6 mg/kg will be administered via intravenous infusion for 6 weeks (two 21-day cycles).

Drug: Trastuzumab emtansine

Interventions

Trastuzumab emtansineDRUG

HER2-targeted antibody drug conjugate of trastuzumab and DM1

Also known as: ado-trastuzumab emtansine; T-DM1; KADCYCLA
Experimental

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female gender;
  • Age ≥18 years;
  • Eastern Cooperative Oncology Group performance status of 0-1;
  • Histologically confirmed invasive breast cancer;
  • Primary tumor greater than or equal to 1 cm diameter, as measured by clinical examination and mammography or ultrasound;
  • Any N;
  • No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);
  • HER2 low or equivocal status in the invasive component of the primary tumor (confirmed by a central certified laboratory prior to study entry)
  • HER2 low expression: 1+/2+ by immunohistochemistry and/or HER2/CEP17 ratio \<2.0 with HER2 copy number \<6.0 signals/cell
  • HER2 equivocal expression: HER2 copy number ≥4.0 and \<6.0 signals/cell;
  • Hematopoietic status:
  • Absolute neutrophil count ≥ 1.0 x 10\^9/L, Platelet count ≥ 100 x 10\^9/L, Hemoglobin at least 9 g/dL;
  • Hepatic status: Serum total bilirubin ≤1 x upper limit of normal (ULN; In the case of known Gilbert's syndrome, a higher serum total bilirubin \[\< 1.5 x ULN\] is allowed), Aspartate aminotransferase and alanine aminotransferase ≤1.5 x ULN, Alkaline phosphatase ≤ 1.5 x ULN;
  • Renal status: Creatinine ≤1.5 mg/dL;
  • International Normalized Ratio ≤1.5 x ULN;
  • +4 more criteria

You may not qualify if:

  • Previous (less than 5 years) or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and carcinoma in situ of the cervix;
  • Patients with a prior malignancy diagnosed more than 5 years prior to study entry;
  • Preexisting peripheral neuropathy ≥ grade 2;
  • Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic oxygen therapy;
  • Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety;
  • Unresolved or unstable serious adverse events from prior administration of another investigational drug;
  • Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
  • Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy other than the trial therapy);
  • 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 or its components;
  • Ejection fraction \<55% or below the lower limit of the institutional normal range;
  • Pregnant or lactating women;
  • Concomitant use of cytochrome P450 3A4 inhibitors or inducers;
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol;
  • Active infection requiring intravenous or oral antibiotics;
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

MaytansineMacrolidesLactonesOrganic ChemicalsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsTrastuzumabAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Jenny C. Chang, M.D.

    Houston Methodist Cancer Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Sponsor-Investigator/Principal Investigator

Study Record Dates

First Submitted

March 18, 2016

First Posted

April 1, 2016

Study Start

March 1, 2016

Primary Completion

April 1, 2019

Study Completion

May 1, 2019

Last Updated

September 14, 2016

Record last verified: 2016-09

Data Sharing

IPD Sharing
Will share

Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Locations

US(1)