Clinical trial NCT02067754: Circulating Free DNA Analysis in Gastrointestinal Cancer, Genitourinary Cancer, Rare Cancer
Official title: Circulating Free DNA Analysis in Gastrointestinal Cancer, Genitourinary Cancer, Rare Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastric Cancer
Keywords: The mutation profiling of circulating free DNA
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2014-02-20
Enrollment: 396
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Pathologically confirmed cancer patients

Brief summary: The investigators planned this study to Patients with histologically confirmed metastatic gastrointestinal cancer, genitourinary cancer , rare cancer with treated any anti-cancer therapy : Extra blood sample collection during routine blood sampling.

Detailed description: Metastasis is a leading cause of cancer related deaths and is also one of the poorly understood aspects of cancer progression. During metastatic outgrowth, a cancer cell from a primary tumor locally invades the surrounding tissue, undergoes intravasation to enter hematogenous circulation and translocates to distant tissues through extravasation, survives and adapts to the foreign microenvironment leading to formation of a macroscopic secondary tumor (Figure 1, Chaffer and Weinberg (2011)). Several cancer therapies have been introduced in the last few decades from cytotoxics to targeted agents. However, these therapies fail to modulate growth of metastatic tumor cells which are often resistant, with most cancer patients succumbing to metastatic disease. There is a key need to further the understanding of metastatic disease in order to develop newer therapies. A central and somewhat unaddressed question is whether this acquisition of malignant traits occurs as an inevitable consequence of tumor progression or as an accidental product thereof. A widely accepted but not so well proven model of primary tumor formation suggests that cancer cells acquire a sequence of genetic and epigenetic alterations, each of which confers one or another form of increased fitness.

Figure 1: The metastatic cascade. Metastasis can be envisioned as a process that occurs in two major phases: (i) physical translocation of cancer cells from the primary tumor to a distant organ and (ii) colonization of the translocated cells within that organ. (A) To begin the metastatic cascade, cancer cells within the primary tumor acquire an invasive phenotype. (B) Cancer cells can then invade into the surrounding matrix and toward blood vessels, where they intravasate to enter the circulation, which serves as their primary means of passage to distant organs. (C) Cancer cells traveling through the circulation are Circulating free DNA. They display properties of anchorage-independent survival. (D) At the distant organ, Circulating free DNA exit the circulation and invade into the microenvironment of the foreign tissue. (E) At that foreign site, cancer cells must be able to evade the innate immune response and also survive as a single cell (or as a small cluster of cells). (F) To develop into an active macrometastatic deposit, the cancer cell must be able to adapt to the microenvironment and initiate proliferation.

It is somewhat accepted that tumors are clonally derived through unregulated growth of single cells that have likely accumulated the necessary number and types of heritable genetic and genomic alterations. Despite the monoclonal origin of cancer, the investigators see many tumors display a large amount of genetic, genomic and signaling heterogeneity. This heterogeneity is also believed to be one of the main drivers of metastasis. This heterogeneity has implications for understanding the disease progression landscape on one hand and diagnosis and treatment decisions on other. It is therefore of direct clinical importance to study the similarities and differences between the primary tumor and metastatic variants

Eligibility criteria: Inclusion Criteria:

* Patients older than 20 years
* Patients with histologically confirmed metastatic gastrointestinal cancer, genitourinary cancer , rare cancer with treated any anti-cancer therapy
* Written informed consent form

Exclusion Criteria:

* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject's safety.

Primary outcomes:
measure: Circulating tumor cell
timeFrame: 1years
Secondary outcomes:
measure: mutation profiling of circulating free DNA
timeFrame: 1years
Other outcomes:
measure: Circulating Free DNA Analysis in Gastrointestinal Cancer, Genitourinary Cancer
timeFrame: From date of start of chemotherapy treatment by Circulating free DNA until the date of first progression or date of death from any cause.
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical center
Study officials:
affiliation: Division of oncologyu, Department of Medicine, Samsung Medical Center
name: Jeeyun Lee, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 1. Lower EE etal. Impact of metastatic ER and PR status on survival. Breast Cancers and Treat. 90. 65-75. 2005. 2. Regitnig P et al. Change of Her-2/neu status in a subset of distant metastases from breast carcibnoma. J Pathol. 203 94) 918-26, 2004. 3. Cristofanilli M. Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781-91. 4. Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janickje F, Jackson S, Gornet T, Cristofanilli M, Pantel K. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13:920-8. 2007 5. Cristofanilli M, Broglio KR, Guarneri V, Jackson S, Fritsche HA, Islam R, Dawood S, Reuben JM, Kaum SW, Lara JM, Krishnamurthy S, Ueno NT, Hortobagyi GN, Valero V. Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden. Clin Breast Cancer 7:471-9, 2007.
citation: Kim ST, Lee WS, Lanman RB, Mortimer S, Zill OA, Kim KM, Jang KT, Kim SH, Park SH, Park JO, Park YS, Lim HY, Eltoukhy H, Kang WK, Lee WY, Kim HC, Park K, Lee J, Talasaz A. Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients. Oncotarget. 2015 Nov 24;6(37):40360-9. doi: 10.18632/oncotarget.5465.