Clinical trial NCT02838836: Tumor Cell and DNA Detection in the Blood, Urine and Bone Marrow of Patients With Solid Cancers
Official title: Tumor Cell and DNA Detection in the Blood, Urine and Bone Marrow of Patients With Solid Cancers
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-small Cell Lung Cancer
Esophageal Cancer
Gastric Cancer
Pancreatic Cancer
Hepatocellular Cancer
Colorectal Cancer
Keywords: Cancer
Circulating tumor cells (CTCs)
Disseminated tumor cells (DTCs)
Circulating tumor DNA (ctDNA)
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2016-07-20
Enrollment: 620
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).

Brief summary: 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.

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.

Hypothesis and Rationale:

CTCs/DTCs and cfDNA isolated from the blood, urine and bone marrow during cancer surgeries 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.

Specific Aims:

CTCs/DTCs and cfDNA isolated from cancer patients will be characterized for genetic alterations and expression of key signaling/proliferation biomarkers and grow in vivo in nude mice.

Study Design:

100 patients undergoing solid cancer surgeries will be recruited for perioperative CTC/DTC/cfDNA isolation from the blood, urine and bone marrow with innovative techniques. In addition, 20 patients undergoing similar surgeries for 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 translational cancer trial 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.

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=20).
* 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.

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: CTC/DTC numbers measured in blood, urine and bone marrow samples will be correlated with patient outcome
timeFrame: 5 years
Secondary outcomes:
measure: ctDNA characteristics will be correlated with survival data
timeFrame: 5 years
Other outcomes:
Locations:
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center, University of Missouri
state: Missouri
Study officials:
affiliation: Ellis Fischel Cancer Center, University of Missouri
name: Jussuf T Kaifi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Suvilesh KN, Nussbaum YI, Radhakrishnan V, Manjunath Y, Avella DM, Staveley-O'Carroll KF, Kimchi ET, Chaudhuri AA, Shyu CR, Li G, Pantel K, Warren WC, Mitchem JB, Kaifi JT. Tumorigenic circulating tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses. Mol Cancer. 2022 Mar 12;21(1):73. doi: 10.1186/s12943-022-01553-5.