Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04874064 |
| Other study ID # |
TRICIA |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 5, 2019 |
| Est. completion date |
June 2023 |
Study information
| Verified date |
May 2021 |
| Source |
Jewish General Hospital |
| Contact |
Adriana Aguilar, PhD |
| Phone |
514-340-8222 |
| Email |
nanaaguilar[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Triple negative breast cancer (TNBC) is the most aggressive of breast cancers and it is
usually treated with chemotherapy even before surgery. In many cases, the chemotherapy
completely "melts" the tumor and these patients do well. When the tumor is not eliminated by
the chemotherapy, the patient receive more chemotherapy after surgery to decrease the chances
of it coming back. Yet many of these patients don't need that extra chemotherapy and will do
well in any case. One of the most exciting recent developments in cancer is the use of
"liquid biopsies". It turns out that the tumor's DNA, RNA and proteins can be detected in
small vesicles found in the patient's blood. Thanks to advances in Artificial Intelligence,
there is now informatics tools to integrate many types of molecular information. Our
industrial partner, MIMs, will apply novel informatics tools to generate a test using all the
molecular information obtained from blood vesicles and tissue that will be able to find out
early if tumor has spread outside of the breast, and how much tumor is left after surgery.
The goal is hope to develop a multi-dimensional test for TNBC patients that can be used to
decide how much treatment they need and if treatment given after surgery is working.
Description:
Rationale: The most aggressive form of breast cancer is triple negative breast cancer (TNBC),
so called because these tumors do not express hormone receptors or HER2 receptor, and
therefore have no readily targetable molecules. Chemotherapy is the only treatment, with
chemoresistance signaling a very poor outcome even in early TNBC. The presence of residual
tumor at surgery (non-pathological complete response or non-pCR) signals chemoresistance and
poor prognosis, with about 30-40% of these patients dying of TNBC within the first 5 years
after surgery. A recent clinical trial showed that the addition of further chemotherapy
(Capecitabine) results in improved survival in these patients with non-pCR, although only
about 15% of such patients do benefit. One of the most urgent unmet needs is to identify
patients who will do well despite non-pCR (so as to avoid extra chemotherapy) and who will do
poorly despite it, and also to identify factors of poor prognosis that may lead to novel
therapeutic strategies in this group.
Current state of advancement of the technology: Until now, no biomarker except BRCA1/2
mutations has demonstrated clinical utility in the treatment of TNBC, likely due to the
complex biology and heterogeneity of the disease. With the recent advances in Artificial
Intelligence methodology, combining and integrating several layers of molecular data to
predict outcome, until now challenging, becomes a reality. The hypothesize is that combining
multi-dimensional data of tumor and plasma EVs can facilitate the development of prognostic
and predictive signatures in this very aggressive disease.
Preliminary data: Thanks to our Q-CROC-03 biopsy driven clinical trial where tumor and plasma
from patients with TNBC resistant to chemotherapy were collected. Whole exome seq data were
translated to generate personalized circulating tumor DNA (ctDNA) assays. Our data shows a
potential prognostic value to the detection of ctDNA after pre-operative chemotherapy. There
is a collaboration established with Rodney Ouellette (ACRI) to isolate and profile
extracellular vesicles (EVs) from plasma.
Objectives: The objective of the present study is to develop signatures of good and poor
outcome as well of tumor response to chemotherapy in TNBCs by integrating multidimensional
profiling of both tumor and liquid biopsies making use of Artificial Intelligence (AI) tools.
Experimental approach: EVs profiling from plasma collected in the Q-CROC-03 trial and the JGH
biobank (prior, during and after chemotherapy treatment) will be performed. Profiling will
include Whole Genome Sequencing (GWS), proteomics, transcriptomics and miRNA analysis. In
collaboration with our industrial partner, My Intelligent Machines (MIMs), experts in
bioinformatics and AI, machine-learning algorithms will be developed to integrate OMICs data
from resistant tumors with matched plasma EVs data and generate a tumor/plasma signature
associated with poor outcome. In parallel, in collaboration with the EXACTIS Innovation
Network, patients recruitment, collection of residual tumors post chemotherapy and matched
serial plasma samples during capecitabine treatment after surgery to perform the validation
of the signature identified, the tumor/EV signature will be associated with patient survival.
Milestones of the proposed project: 1. Profiling of EVs from plasma. 2. Profiling of
chemoresistant tumors 3. Development of algorithms to integrate multidimensional data from
tumor and EVs.
The developed signatures will be IP protected. Academic and industrial partners will have
shared IP (respective % to be determined). Prognostic tests will be developed on identified
biomarkers and distributed through MIMsOmic Platform. MIMsOmic is an AI-powered platform
commercialized by MIMs and enabling an easy, efficient and cost-effective delivery of
clinical tests involving Omic data analysis.
The present project will develop a biomarker signature of poor prognosis for the most
aggressive type of breast cancer. This signature will allow the identification of patients
who should not be treated with post-surgery chemotherapy, and avoid unnecessary exposure to
the toxicity associated with this drug.
