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Proposal 1688

Title of the Proposed Research

Translational data from LPT109096 to assess the impact of HER2-targeted therapies on HER-family and stem cell marker expression.

Lead Researcher

Denis Collins

Affiliation

National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.

Funding Source

Dr. Stephen Madden, the named statistician, holds a faculty position at the Royal College of Surgeons in Ireland and is a long term collaborator of Dr. Collins. Dr. Virginia Espina and Dr. Lance Liotta were part of the team that originally generated the LPT109096 RPPA dataset and will be advising on technical aspects and reviewing and editing the final manuscript. Dr. Espina and Dr. Liotta are a faculty members at George Mason University.

Potential Conflicts of Interest

Summary for all Researchers and Statistician
Dr. Denis Collins
Board memberships: None
Consultancies: None
Employments: Dublin City University
Grants/grants pending: Current: Roche Postdoctoral Fellowship, Past: Irish Research Council Enterprise Partnership Scheme Postdoctoral Fellowship co-funded by Roche Products (Ireland) Ltd. (2011-2013)
Patents (planned, pending or issued): None
Royalties: None
Stocks or shares (including options): NoneBoard memberships: none
Consultancies: none
Employments: George Mason University
Grants/grants pending: none with any overlap related to Lapatinib or Trastuzumab
Patents (planned, pending or issued):
USPTO Patent 8,497,137 Smart hydrogel particles for biomarker harvesting
USPTO Patent 8, 460,859 B2: Tissue preservation and fixation method
USPTO Patent 8,628,931 mTOR pathway theranostic
USPTO Patent 9,012,240 Hydrogel nanoparticle based immunoassay
USPTO Patent 9,029,076 Tissue preservation and fixation method
USPTO Patent 9,086,414 Phosphorylated C-ErbB2 as a superior predictive theranostic marker for the diagnosis and treatment of cancer
USPTO Patent 9,096,833 Methods of treating pre-malignant ductal cancer with autophagy inhibitors

Royalties: Ceres Nanosciences and Theranostics Health are licensees for patents/technology developed by me and others at George Mason University. As a university employee, I am entitled to royalties from these patent licenses. The total monetary value per year I have received for these royalties has been $0-$4,999.00 USD.
Stocks or shares (including options): I held stock options in Theranostics Health from 2010 – June 2016; the stock options have expired, and were never exercised. Royalties: Ceres Nanosciences and Theranostics Health are licensees for patents/technology developed by me and others at George Mason University. As a university employee, I am entitled to royalties from these patent licenses. The total monetary value per year I have received for these royalties has been $0-$4,999.00 USD.
Stocks or shares (including options): I held stock options in Theranostics Health from 2010 – June 2016; the stock options have expired, and were never exercised.

Data Sharing Agreement Date

25 October 2017

Lay Summary

Targeted therapies are drugs that are designed to affect cancer cells only. This study is about two types of targeted therapies used in breast cancer, antibody therapies and tyrosine kinase inhibitors (TKIs).

Antibody therapies can work in two ways. They can kill cancer cells directly or they can recruit white blood cells to kill cancer cells. TKIs can only kill cancer cells directly.

Herceptin is an antibody therapy that is used to treat breast cancer in ~600 women/year in Ireland. Unfortunately, not all patients respond to Herceptin. In addition, Herceptin can stop working in those patients that do respond first time round. If Herceptin stops working, breast cancer is said to have developed resistance to Herceptin.

Herceptin resistance is a major problem in the clinic. There is now interest in giving the combination of TKIs and Herceptin to try and overcome Herceptin resistance. The idea is that the TKIs could improve the white blood cell response to Herceptin.

Dr. Collins has carried out experiments and tested the combination of multiple TKIs and Herceptin in the lab with promising results.

Dr. Espina’s group has analysed tumour biopsies from patients on a clinical trial who have received a TKI and Herceptin. Dr. Espina’s results are extremely relevant to Dr. Collins’ work as they would allow a comparison of results obtained in the lab with results from patients in the clinic.

This proposal is a request by Dr. Collins to access Dr. Espina’s experimental results and clinical data for use in a publication that he is preparing.

The main questions this study will try to answer are:

1) Does a combination of TKI and Herceptin do the same thing to cancer cells in patients as they do in the lab?
2) Are changes in the cancer cells caused by the TKI and Herceptin associated with better or worse outcome in the patients?
3) What does a combination of TKI and Herceptin do to Herceptin resistant cancer cells in patient tumours?

Dr. Collins will also examine any links between changes caused by the TKI and Herceptin combination and other characteristics of the tumours from patients on LPT109096 (such as tumour size).

The team associated with this proposal have the necessary expertise to carry out this project. Dr. Collins is a scientist who specialises in targeted therapies. Dr. Madden is a statistician who has responsibility for analysing the data. Dr. Espina and Dr. Liotta are the team that originally generated the data that Dr. Collins is requesting access to (LPT109096).

The results will be presented to the public and patient groups through Cancer Clinical Research Trust (Irish Charity No.: CHY12210) events. Once published, the work will be available internationally and publicised through the Irish Cancer Society, Dublin City University and authors’ social media platforms.

Study Data Provided

NOVARTIS-LPT109096: Phase II Randomized Trial of Neoadjuvant Trastuzumab and/or Lapatinib plus Chemotherapy (Sequential FEC75 and Paclitaxel) in Women with ErbB2- (HER2/neu-) Overexpressing Invasive Breast Cancer

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.