Clinical trial NCT03551951: Tumor Cell and DNA Detection in the Blood, Urine, and Bone Marrow
Official title: Tumor Cell and DNA Detection in the Blood, Urine and Bone Marrow of Patients with Solid Cancers and Subjects Undergoing Lung Cancer Screening
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non Small Cell Lung Cancer
Esophageal Cancer
Gastric Cancer
Pancreatic Cancer
Hepatocellular Cancer
Colorectal Cancer
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
Collaborators: name: Harry S. Truman Memorial Veterans' Hospital
First posted: 2018-06-11
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with the diagnosis of a solid cancer of all stages will be included (lung, esophageal, stomach, bile duct/pancreas, colorectal, melanoma, sarcoma).

Lung cancer screening subjects will also be included (as defined above)

Total recruitment: 320

Brief summary: Patients with resectable solid primary cancers and even limited number of metastases are potentially curable. However, most patients develop recurrences despite surgery. Also, early detection of lung cancer with low dose CT screening may cure patients at an early stage. Circulating and disseminated tumor cell (CTC/DTC) and circulating cell-free (cf) DNA isolation from the blood, urine and bone marrow will increase understanding of cancer spread and advance knowledge to develop individualized therapies and improve screening.

Detailed description: Background: Patients with resectable solid primary cancers and even limited number of metastases are potentially curable. However, most patients develop recurrences despite surgery. Circulating and disseminated tumor cell (CTC/DTC) and circulating cell-free (cf) DNA isolation from the blood, urine and bone marrow will increase understanding of cancer spread and advance knowledge to develop individualized therapies. These liquid biomarkers might also be suitable for screening purposes and early detection of in high risk subjects for lung cancer.

Hypothesis and Rationale: CTCs/DTCs and cfDNA isolated from the blood, urine and bone marrow undergo pheno- and/or genotype changes. CTCs/DTCs have potential for dissemination and tumor growth in vivo. Investigating the biology of liquid biomarkers in the blood, urine and bone marrow will significantly increase understanding of cancer biology of early and advanced stages.

Specific Aims: CTCs/DTCs and cfDNA will be quantified and characterized for genetic alterations and expression of key signaling/proliferation biomarkers and grow in vivo in nude mice.

Study Design: 100 cancer patients will be recruited for CTC/DTC/cfDNA isolation from the blood, urine and bone marrow with innovative techniques. Bone marrow will be drawn only perioperatively in cancer patients undergoing anesthesia for surgery. 200 high-risk individuals undergoing lung cancer screening with a low dose CT will also be included for blood and urine collection to test the usefulness of these liquid biomarkers for early detection of lung cancer. In addition, 20 individuals with benign disease will also be included as controls. CTCs/DTCs, cfDNA and cancer tissue pheno- and/or genotype analysis will be performed with different innovative techniques. Furthermore, CTCs/DTCs will be enriched, cultured and characterized. Tumor growth potential will be studied in nude mice.

Relevance: This study addresses fundamental aspects of cancer disease being the cause of death in 1 out of 4 persons in the US. Innovative CTCs/DTCs characterization can shed light on the tumor biology, and identify therapy targets. Results of this study can be fundamentally important to understanding cancer spread and development of personalized therapies, and improve early detection.

Eligibility criteria: Inclusion Criteria:

* Subjects older than 18 years.
* Subjects of all genders and ethnicities.
* Subjects with the diagnosis of a solid cancer (n=100) of all stages will be included (lung, esophageal, stomach, bile duct/pancreas, colorectal, melanoma, sarcoma).
* Ten patients with no present suspicion and no previous history of any cancer (except basal cell cancer of the skin) that undergo surgeries for other benign indications will serve as controls (n=10).
* In patients undergoing surgery for cancer the histopathology should preferably be pathologically proven by a previous or novel biopsy. Yet, patients with a high cancer suspicion by radiology and clinical picture that undergo cancer surgery will not be excluded. No additional biopsies, testing or interventions will be performed for the purpose of this study if the medical treatment will not require it.
* Subjects must be capable of giving informed consent.
* Lung cancer screening eligibility criteria (n=100): 55-80 years old, \>30 pack years smoking history, and current smoker or have quit within the last 15 years)

Exclusion Criteria:

* Pregnant women.
* Subjects with the concurrent diagnosis of an active secondary (synchronous) malignancy besides basal cell carcinoma of the skin will be excluded, if there is evidence of disease burden or if the patient is currently being treated with chemotherapy.
* Subjects with a hemoglobin of \<8g/dl in the morning of the procedure will be excluded.
* In subjects who require intraoperative transfusions of \>4 units of red packed blood cells (RPBCs), no further blood will be drawn for CTC/DTC/cfDNA analysis during surgery or on postoperative day 1.
* In patients with coagulation disorders that could lead to significant bleeding (such as hemophilia, significant thrombocytopenia) requiring prophylactic administration of coagulative products, no bone marrow aspiration will be performed.

Primary outcomes:
measure: Number of CTC/DTC in blood
timeFrame: At baseline
measure: Number of CTC/DTC in urine
timeFrame: At baseline
measure: Number of CTC/DTC in bone marrow
timeFrame: At baseline
measure: Quantity of cfDNA in blood
timeFrame: At baseline
measure: Quantity of cfDNA in urine
timeFrame: At baseline
measure: Quantity of cfDNA in bone marrow
timeFrame: At baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Columbia
country: United States
facility: Harry S Truman Veterans Memorial Hospital
state: Missouri
Study officials:
affiliation: University of Missouri Health Care
name: Jussuf T Kaifi, MD
role: PRINCIPAL_INVESTIGATOR
References: