Presurgical Therapy With Lapatinib to Explore Molecular Determinants of Response to EGFR/erbB2 Targeted Therapy

December 9, 2015 updated by: University of Pennsylvania

The purpose of this study is to see what kinds of breast tumors will respond to lapatinib. Lapatinib is an experimental medicine which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

Status

Withdrawn

Conditions

Breast Cancer

Intervention / Treatment

Drug: Lapatinib

Study Type

Interventional

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19104
    - Abramson Cancer Center of University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Histologically or cytologically-confirmed by either core or fine needle biopsy primary invasive carcinoma of the breast;
AJCC T2-T3 disease (>2.0 cm without chest wall or skin invasion) by at least one imaging modality (either mammogram, ultrasound, or MRI) - entry criteria is based on radiologic staging and not final pathologic staging;
ECOG performance status 0-1 (Karnofsky ≥ 70%
Any lymph node status, hormone receptor status, and level of erbB2 expression
No prior chemotherapy, hormonal therapy or radiation therapy to the affected breast for current or previous malignancy;
Cardiac ejection fraction >50% or within the institutional range of normal;
Patients must have normal organ and marrow function defined as: Leukocyte count >3000/uL; Absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets > 100,000/mm3, and hemoglobin ≥ 8 gm/dl; Serum creatinine ≤ 1.5 times ULN, or 24-hour creatinine clearance ≥ 75 cc/min; Serum bilirubin ≤ 1.5 times ULN; SGOT ≤ 2.5 times ULN; alkaline phosphatase ≤ 2.5 ULN times ULN.
The effects of lapatinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Ability to understand and the willingness to sign written informed consent document.

Exclusion Criteria:

AJCC T1, T4, or stage 4 disease;
Patients may not have undergone incisional or excisional biopsy of their tumor;
Patients may not be receiving any other investigational agents;
Absolute contraindication to MRI imaging (cardiac pacemaker or any non-removable metallic foreign object in the body);
On chronic therapy with any known inducer or inhibitor of CYP3A4
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant or lactating women are excluded from this study because lapatinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in downstream effector levels in biologic responders to lapatinib as determined by degree of change in proliferation and apoptosis compared to biologic non-responders. Time Frame: Study completion	Study completion

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe the biologic response rate, defined by induction of apoptosis, to Lapatinib in a pre-surgical, treatment-naïve breast cancer population. Time Frame: Study completion	Study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

Principal Investigator: Angela DeMichele, M.D., University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Anticipated)

May 1, 2009

Study Completion (Anticipated)

December 1, 2009

Study Registration Dates

First Submitted

June 21, 2006

First Submitted That Met QC Criteria