Tumor Specific Plasma DNA
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|ClinicalTrials.gov Identifier: NCT01617915|
Recruitment Status : Active, not recruiting
First Posted : June 13, 2012
Last Update Posted : January 23, 2019
In 2011, there was an estimated 233,000 cases of invasive breast cancer, and 39,970 deaths from breast cancer in the United States. The vast majority of patients are diagnosed with Stage I-III resectable and potentially curable disease, and for these patients, the most pressing questions are whether adjuvant endocrine or chemotherapy are indicated, and if so, how to determine whether these treatments are working. Adjuvant systemic therapy reduces relative recurrence rates by 30-50%, depending on the age of the patient and tumor characteristics. However, patients with early stage disease often do not bear measurable markers of disease such as an elevated cancer antigen 27-29 (CA27.29) or circulating tumor cells. Patients with early stage breast cancer are typically treated with adjuvant therapy based on historical evidence showing that such therapy prolongs survival in this population.
Lung cancer is the most common malignancy and the leading cause of cancer-related death in the U.S. Approximately 220,000 new cases of lung cancer are diagnosed in the U.S. every year. Unfortunately, lung cancers are often diagnosed at later stages than breast cancer, due in part to little/no effective screening for lung cancer. As with breast cancer, patients are commonly treated with chemotherapeutic agents, but treatment regimens can take several weeks to months to elicit clinically detectable anti-tumor effects. A biomarker to assess early tumor response to therapy would benefit this patient population.
The contents of dying tumor cells can be detected in the bloodstream, and this may be enhanced by the leaky vasculature of solid tumors. Protein biomarkers of tumor cell death are difficult to detect due to the complex nature of plasma and the lack of technical sensitivity. In contrast, DNA is easier to detect through polymerase chain reaction (PCR) amplification. Indeed, circulating tumor DNA has been detected in plasma from patients with osteosarcoma, breast cancer, and colorectal cancer. Until recently, it was impractical to develop an assay to routinely quantify circulating tumor DNA due to heterogeneity between patients and tumors. Advances in genomic technology now permit sequencing a tumor genome to identify patient-specific genomic aberrations. Major genomic alterations (i.e., insertions, amplifications, deletions, inversions, translocations) can be readily detected using PCR primers which will recognize tumor DNA but not normal DNA.
While this strategy may be generally applicable to diverse types of solid tumors, two issues are apparent in breast cancer. Firstly, the incidence of chromosomal rearrangements varies widely. Whole-genome sequencing of 15 breast tumors revealed a range of 1-231 major genomic alterations (mean= 68), where 2 tumors had 1 alteration, and 9 tumors had > 20 alterations. Single-base point mutations are more common but difficult to reliably detect using PCR. Therefore, the investigators must consider that a small subset of patients may have a limited number of genomic alterations available for this assay. Secondly, intratumoral heterogeneity may mean that some genomic alterations are not present in every tumor cell. Such heterogeneity has been inferred from FISH and immunohistochemistry (IHC) studies for many years, and is now being verified at the genomic level. The investigators must consider that only a subpopulation of tumor cells may be sensitive to cytotoxic therapy, so changes in the levels of circulating tumor DNA may only be reflected with analysis of genomic alterations specific to the sensitive cells.
|Condition or disease|
|Breast Cancer Lung Cancer|
|Study Type :||Observational|
|Actual Enrollment :||6 participants|
|Official Title:||Tumor Specific Plasma DNA|
|Study Start Date :||October 2012|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
- Circulating tumor levels correlation to response [ Time Frame: 6 months ]To determine whether acute increases in the levels of circulating tumor DNA correlate with response to chemotherapy in patients with breast cancer.
- Circulating tumor DNA following surgery [ Time Frame: 6 months ]To determine whether the levels of circulating tumor DNA acutely decrease following surgical resection of a primary breast tumor.
- To determine optimal timing for detection of circulating tumor DNA [ Time Frame: 6 months ]To determine the optimal timing for detection of changes in levels of circulating tumor DNA.
- Circulating tumor DNA detection following surgery [ Time Frame: 6 months ]To determine whether circulating tumor DNA detectable at 1-2 weeks following surgical resection of a primary tumor predicts disease recurrence.
- Circulating tumor DNA correlation with pathologic complete response [ Time Frame: 6 months ]To determine whether the fall in circulating tumor DNA correlates with pathologic complete response to neoadjuvant chemotherapy in patients with early-stage breast cancer, or with clinical response to chemotherapy in patients with locally advanced or metastatic breast cancer..
- Circulating tumor DNA correlation with clinical evidence of disease recurrence or progression [ Time Frame: 6 months ]To determine whether circulating tumor DNA levels increase prior to clinical evidence of disease recurrence or progression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01617915
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Gary N Schwartz, MD||Dartmouth-Hitchcock Medical Center|