IRB Study Number 24-1071
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
Part 1:
To establish the rate of evaluable tissue submissions, defined as the proportion of participants for whom available material from their FFPE diagnostic breast biopsy is sufficient for creation of a participant-specific bespoke ctDNA assay.
Part 2:
To validate the association of serially measured ctDNA status, starting at the first blood draw following completion of cytotoxic adjuvant therapy for those receiving adjuvant cytotoxic therapy, and at the post-surgery blood draw for those not receiving cytotoxic adjuvant therapy, with distant recurrence-free interval (dRFI).
To validate the association of ctDNA positivity detected at the first blood draw following completion of cytotoxic adjuvant therapy for those receiving adjuvant cytotoxic therapy, and at the post-surgery blood draw for those not receiving adjuvant cytotoxic therapy, with dRFI.
Secondary Objectives
Part 1:
To assess the association of ctDNA status collected at various timepoints during neoadjuvant therapy (pretreatment baseline, early-neoadjuvant therapy, post-neoadjuvant therapy/pre-surgery) with pathologic complete response (pCR) status.
To assess the prevalence of tumor mutations and germline variants of interest.
Part 2:
To assess the association of ctDNA status at baseline, early-neoadjuvant therapy, post-neoadjuvant therapy/pre-surgery, post-surgery/pre-cytotoxic adjuvant therapy (if administered), and post-cytotoxic adjuvant therapy (if administered) time points with dRFI, with and without adjustment for clinicopathologic and genomic risk factors.
To assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of post-neoadjuvant therapy/pre-surgery ctDNA status for pCR status.
To assess the sensitivity and specificity of post-surgery/post-cytotoxic adjuvant therapy (if administered) ctDNA status measured serially and at the post-surgery/post-cytotoxic adjuvant therapy (if administered) time point for subsequent distant recurrence.
To assess time from first post-treatment positive ctDNA to clinically detected distant recurrence in participants who had a positive ctDNA result at or following the post-surgery/post-cytotoxic adjuvant therapy (if administered) completion time point.
To assess the association of ctDNA clearance, defined as change from positive baseline ctDNA result to negative ctDNA result prior to surgery and post-surgery/pre-cytotoxic adjuvant therapy (if administered), with pCR and dRFI.
To assess the association of ctDNA, both serially and at the post-surgery/post-cytotoxic adjuvant therapy (if administered) completion time point with the endpoints of recurrence-free interval (RFI), invasive breast cancer-free survival (IBCFS), event-free survival (EFS), and overall survival (OS).
Inclusion Criteria
The participant or a legally authorized representative must provide study-specific informed consent prior to study entry.
The participant must be ≥ 18 years of age.
ECOG performance status 0 or 1.
Histologically confirmed invasive carcinoma of the breast.
Planned neoadjuvant therapy which includes cytotoxic chemotherapy.
Tumor size ≥ 2.1 cm in greatest diameter.
Unifocal or multifocal cancer documented to be the same histologic clinical subtype.
Clinically node positive or if node negative, any one of the following:
a. TNBC or HER2+ subtype
b. HR+/HER2-negative with at least one of the following:
i. High tumor grade (G3)
ii. Ki67 index of 20% or higher
iii. High genomic risk (Oncotype DX (ODX) Breast Recurrence Score of > 25, MammaPrint® High, etc.)
Willing and able to comply with the study requirements, which includes the collection of approximately 34 cc (2.5 Tablespoons) of blood for each research blood draw.
Available residual tissue for testing from diagnostic biopsy from the breast or an involved ipsilateral lymph node for submission to create a bespoke ctDNA assay.
Exclusion Criteria
Definitive clinical or radiologic evidence of metastatic disease.
Initiated neoadjuvant therapy for current breast cancer diagnosis.
Synchronous diagnosis of another invasive cancer, other than this breast cancer, except for non-melanoma skin cancers.
Completed all therapy (including endocrine therapy) <5 years ago for any previous invasive solid organ malignancy (with exception of non-melanoma skin cancers) including prior breast cancer. Individuals with a prior history of noninvasive (in situ) carcinomas may participate if they have received definitive treatment.
Completed all therapy for any previous hematologic malignancy < 5 years ago.
Multicentric or contralateral invasive breast cancers.
Known pregnancy at time of enrollment.
Prior solid organ transplant.
Prior allogeneic hematopoietic stem cell transplant.
