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This is a prospective phase 2 study to use Functional Precision Oncology (FPO) to predict, prevent and treat early metastatic recurrence in subjects with HR-low/Her2 negative or triple negative breast cancer.
Full description
The aim of this clinical trial is to extend the findings of the investigators' first observational clinical study titled "Towards personalized medicine: patient derived breast tumor grafts as predictors of relapse and response to therapy" (TOWARDS-I). In TOWARDS-II, the investigators will develop patient derived models (PDMs), comprising patient derived xenografts (PDXs) and organoids (PDO and PDxO), from patients newly diagnosed with local or locally advanced hormone receptor-low/Her2 negative or triple negative breast cancer. The investigators will prospectively evaluate the correlation between PDX engraftment with recurrence. Using PDMs, the investigators will perform genomic studies and functional drug screens (FPO). Upon disease recurrence, the investigators will return the results to the physician with the intent to inform treatment selection.
Enrollment
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Volunteers
Inclusion and exclusion criteria
Registration: Pre-tumor Collection Eligibility Participant Inclusion Criteria
Subject aged ≥ 18 years.
Subject has Stage I-III disease.
Histologically or cytologically confirmed invasive breast carcinoma that is triple negative (TNBC) or hormone receptor (HR)-low/Her2 negative
--TNBC is defined as:
HER2 expression 0 or 1+ on immunohistochemistry (IHC) or non-amplified (defined as HER2/CEP17 ratio <2 or copy number <6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, negative HER2 expression must be confirmed by FISH. Pathologic diagnosis of TNBC (negative HER2 status by cytogenetics, <1% of cells stained positive for estrogen receptor (ER) by IHC, and <1% of cells stained positive for progesterone receptor (PR) by IHC).
--HR-low/Her2(-) is defined as:
HER2 expression 0 or 1+ on IHC or non-amplified (defined as HER2/CEP17 ratio <2 or copy number <6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, negative HER2 expression must be confirmed by FISH.1-10% of cells stained positive for ER by IHC, and/or 1-10% of cells stained positive for PR by IHC).
Primary tumor OR local lymph node metastasis that is ≥ 1.5 cm. Patients with inflammatory breast cancer are eligible, regardless of tumor size. Patients with multifocal or multicentric breast cancer are eligible so long as ALL tumors biopsied per standard of care guidelines and/or investigator discretion meet receptor status criteria, and at least one tumor measures ≥ 1.5 cm.
Patient is considered for preoperative cytotoxic chemotherapy per standard of care or in the context of a separate, ongoing clinical trial.
Patient has not received any prior therapy for thier breast cancer.
Willing and capable (per treating investigator's assessment) to undergo baseline tumor material collection from the primary tumor or lymph node metastasis.
Patient can safely undergo tumor collection:
Life expectancy of ≥ 12 months as assessed by the treating investigator.
ECOG Performance Status ≤ 2.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
No prior history of local or locally advanced hormone receptor positive (ER and/or PR expression >10% on immunohistochemistry) breast cancer, unless the following conditions are met:
Physician Inclusion Criteria
Participant Exclusion Criteria
Evidence of metastatic breast cancer
ER and/or PR expression >10% on immunohistochemistry
Her2(+) and/or Her2-amplified breast cancer. HER2 expression 3+ on IHC or amplified (defined as HER2/CEP17 ratio ≥2 or copy number >6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, reflex FISH must be performed to determine eligibility.
Patient has bilateral breast cancer
Patient received any anti-cancer therapy or any investigational therapy prior to study entry and collection of tumor.
--Treatment includes: neoadjuvant therapy, radiation therapy, chemotherapy, bisphosphonates for an indication other than osteopenia/osteoporosis, and/or hormonal therapy administered for the currently diagnosed primary breast cancer prior to study entry. Hormonal therapy for a prior diagnosis of a hormone receptor-positive breast cancer us allowed.
The diagnosis of another malignancy, unless the patient is considered disease-free for ≥5 years before study entry. Patients are eligible if diagnosed and treated for carcinoma in situ of the cervix, melanoma in situ, colon cancer in situ, ductal carcinoma in situ, and basal and/or squamous cell carcinoma of the skin, early stage papillary thyroid cancer, and other low risk malignancies per investigator discretion.
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
Cardiovascular disorders:
Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [subjects may not receive the drug through a feeding tube], social/ psychological issues, etc.)
Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
Primary purpose
Allocation
Interventional model
Masking
80 participants in 2 patient groups
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Central trial contact
Janna Espinosa
Data sourced from clinicaltrials.gov
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