Stage IV Colorectal CancerNCT01722903
Detection of CTCs in Patients Undergoing Surgery for Stage IV Colorectal Cancer
An observational study of Stage IV Colorectal Cancer and Liver Metastases, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. About 90% of CRC related deaths are due to metastatic spread-mostly to the liver and lungs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Colorectal Cancer, Liver Metastases, Lung Metastases
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Jun 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 50 patients with colorectal cancer metastatic to liver and/or lungs will be enrolled. Patients must be older than 18 years. No healthy volunteers/control group will be included.
Who may be able to join
- Subjects older than 18 years will be included.
- Subjects with colorectal primary carcinomas metastatic to the liver and/or lungs who will undergo a synchronous resection of both primary tumor and liver metastases will also be enrolled.
- Subjects of all genders and ethnicities will be included.
- Subjects with the diagnosis of stage IV primary CRC will be included if metastases are limited to liver and/or lungs at the time of primary surgery.
- The histopathology of the CRC primary tumor must be documented to be adenocarcinoma.
- Subjects with the diagnosis of syn- and metachronous liver and/or lung metastases from colorectal carcinoma will be included, as long as metastases at both sites are resectable by minimal invasive or conventional approach (usually sequentially and not simultaneously).
- Liver and lung metastases must be defined according to radiological criteria. In case of doubt on radiologic findings, percutaneous biopsy will have to be obtained.
- Subjects must be capable of giving informed consent or have an acceptable surrogate capable of giving legally authorized consent on the subject's behalf.
Who cannot join
- Subjects with the concurrent diagnosis of an active second malignancy besides basal cell carcinoma of the skin will be excluded, if there is evidence of disease burden or the patient is currently treated with chemotherapy.
- Subjects with a Hemoglobin of <8g/dl in the morning of the procedure will be excluded.
- In subjects who had needed intraoperative transfusions >4 units of RPBCs, no further blood will be drawn for CTC analysis.
- Pregnant women will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
MS Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Perioperative Detection and Characterization of Circulating Tumor Cells in Patients Undergoing Colorectal Cancer Liver and Lung Metastasectomy
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. About 90% of CRC related deaths are due to metastatic spread-mostly to the liver and lungs. With adequate multidisciplinary patient selection, CRC liver and lung metastasectomy significantly improves survival and offers the best chance for a cure. However, patients with limited lung or liver metastases are clinically underserved and poorly scientifically studied. The individual indication for resection and the decision making for adjuvant systemic therapies remains a challenge. More sensitive techniques to detect occult disease are needed for metastatic CRC (mCRC) patients, and perioperative analysis of circulating tumor cells (CTCs) may provide an outstanding opportunity to develop such innovative methods. We hypothesize that CTCs are enriched during CRC liver and/or lung metastasectomy, and that they can be isolated and characterized in an attempt to identify novel therapeutic targets.
CTCs are believed to be causing metastasis and may provide a non-invasive alternative to organ biopsies for the detection, characterization and monitoring of solid cancers. CTC numbers have been shown to be a strong predictor of Progression Free Survival and Overall Survival for mCRC patients. The CellSearch system (Veridex LLC, Ratinas, NJ, USA) currently is the only FDA approved test for the evaluation of CTC numbers in metastatic breast, prostate and colorectal cancer. However, the rarity of CTCs in the blood leads to limited capture efficiency and the CellSearch system fixes cells, preventing further molecular characterization of CTCs by functional assays and primary cell culture. In this protocol the CellSearch system will be compared to a new technology, called the Flexible Micro Spring Array (FMSA) device, developed by Dr. Zheng, Department of Bioengineering, Penn State University, University Park. This novel approach enables size-exclusion based filtration for viable CTC enrichment. The FMSA device is inexpensive, works rapidly, and retains viable CTCs for further biological study. Using both the CellSearch system and the FMSA device, we will determine the kinetics of CTC shedding into circulation, develop an effective system for isolation, enumeration, and further enrichment CTCs, and use this system to find characteristics of different CTC populations.
Read the detailed description
More sensitive techniques to detect occult disease are needed for metastatic CRC (mCRC) patients, and perioperative analysis of circulating tumor cells (CTCs) may provide an outstanding opportunity to develop such innovative methods.
Determine kinetics of CTC shedding into the circulation: Perioperative CTC detection has the potential to explain how and when CTCs are shed into the blood. Findings could explain the nature of CTCs with important impact on understanding metastatic spread and relevant clinical applications.
Since this protocol includes blood draws at multiple time points at different distances from the metastases, results could further clarify if the rarity or absence of CTCs in the peripheral blood of some mCRC patients can be explained by dilution. Comparison of patients with CRC liver to lung metastases might help explain different patterns of organ spread. Results of this study could establish CTCs as a prognostic biomarker identifying candidates who will benefit from metastasectomy or for those who are candidates for additional or palliative systemic treatments because of a high risk for later recurrence.
- Develop effective system for isolation, enumeration, enrichment and further characterization of live CTCs: One of the current issues of CTC analysis is the enrichment of those rare cells from blood. We plan to analyze perioperatively drawn blood using the flexible micro spring array (FMSA) device. The FMSA mitigates the stresses experienced by CTCs during their isolation from blood and enables viable capture. The geometric design and filtration pressures have been optimized to maximize capture efficiency, enrichment against leukocytes, and tumor cell viability. Peripheral blood as well as blood from the direct tumor environment (taken from the OR suctioning system) will be analyzed to compare the sensitivity of the FMSA and CellSearch device. Since the FMSA allows for isolation of live CTCs, they will be processed for further single cell characterization.
- Find characteristics of different CTC populations: We hypothesize that CTCs will be enriched for cancer stem cell markers as well as markers for poor prognosis and aggressive tumor growth. Our novel approach to screen and quantify a panel of biomarkers simultaneously with analysis of the CTC markers utilized by the CellSearch system to analyze of CTCs is unique. We view our assays as potential "liquid biopsies" that can screen for markers of prognosis, sensitivity to chemotherapy, response to therapy, as well as for proteins involved in proliferation, apoptosis, and immune response.
Furthermore, we plan to perform single cell analysis of gene mutations and gene expression. Next generation genomic sequencing of single CTCs may allow us to determine a genetic signature for colorectal CTCs and to identify novel biomarkers for CTC detection, disease monitoring, and therapeutic efficacy. Furthermore, the extent of heterogeneity among initially isolated CTCs, which can be compared to the primary tumor and CTCs growing in vitro, will be studied. Single CTC analysis has the potential to identify novel gene and signal transduction pathways that are activated in CTCs and to compare this genomic profile to that of the primary tumor and patient metastasis. Single cell genomic analysis in CTCs is highly innovative and will provide important information for disease monitoring as well as shed light on the underlying biology of CTCs.
- Keywords
- colorectal cancer, liver metastases, lung metastases
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Stage IV colorectal cancer | CTCs will be drawn during liver and/or lung metastasectomy for colorectal cancer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantity of CTCs isolated during liver and/or lung metastasectomy
Define in which quantity CTCs are retrievable from different blood compartments and lost blood during CRC liver and lung metastases surgery using the Veridex CellSearch system and FMSA filter device
Measured: 1 year
Secondary outcomes (1)
Overall survival
Determine relationship of CTC numbers overall survival after CRC liver and lung metastases surgery
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2013
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage IV Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Angela Lehman, Milton S. Hershey Medical Center
- Investigators
- Jussuf T Kaifi, MD PhD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01722903
- Sponsor's protocol ID
- 39748EP
- Status last verified
- Sep 2016
- First submitted
- 5 Nov 2012
- Last updated
- 13 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Kaifi JT, Kunkel M, Das A, Harouaka RA, Dicker DT, Li G, Zhu J, Clawson GA, Yang Z, Reed MF, Gusani NJ, Kimchi ET, Staveley-O'Carroll KF, Zheng SY, El-Deiry WS. Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: a prospective trial with different detection techniques. Cancer Biol Ther. 2015;16(5):699-708. doi: 10.1080/15384047.2015.1030556.
PubMed 25807199
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Detection and Characterization of Circulating Tumor Cells in Patients Undergoing Colorectal Cancer Liver and Lung Metastasectomy
- ClinicalTrials.gov ID
- NCT01722903
- Acronym / sponsor ID
- 39748EP
- Keywords
- colorectal cancer, liver metastases, lung metastases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- May 2013 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 7 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. About 90% of CRC related deaths are due to metastatic spread-mostly to the liver and lungs. With adequate multidisciplinary patient selection, CRC liver and lung metastasectomy significantly improves survival and offers the best chance for a cure. However, patients with limited lung or liver metastases are clinically underserved and poorly scientifically studied. The individual indication for resection and the decision making for adjuvant systemic therapies remains a challenge. More sensitive techniques to detect occult disease are needed for metastatic CRC (mCRC) patients, and perioperative analysis of circulating tumor cells (CTCs) may provide an outstanding opportunity to develop such innovative methods. We hypothesize that CTCs are enriched during CRC liver and/or lung metastasectomy, and that they can be isolated and characterized in an attempt to identify novel therapeutic targets.
CTCs are believed to be causing metastasis and may provide a non-invasive alternative to organ biopsies for the detection, characterization and monitoring of solid cancers. CTC numbers have been shown to be a strong predictor of Progression Free Survival and Overall Survival for mCRC patients. The CellSearch system (Veridex LLC, Ratinas, NJ, USA) currently is the only FDA approved test for the evaluation of CTC numbers in metastatic breast, prostate and colorectal cancer. However, the rarity of CTCs in the blood leads to limited capture efficiency and the CellSearch system fixes cells, preventing further molecular characterization of CTCs by functional assays and primary cell culture. In this protocol the CellSearch system will be compared to a new technology, called the Flexible Micro Spring Array (FMSA) device, developed by Dr. Zheng, Department of Bioengineering, Penn State University, University Park. This novel approach enables size-exclusion based filtration for viable CTC enrichment. The FMSA device is inexpensive, works rapidly, and retains viable CTCs for further biological study. Using both the CellSearch system and the FMSA device, we will determine the kinetics of CTC shedding into circulation, develop an effective system for isolation, enumeration, and further enrichment CTCs, and use this system to find characteristics of different CTC populations.
Detailed description
More sensitive techniques to detect occult disease are needed for metastatic CRC (mCRC) patients, and perioperative analysis of circulating tumor cells (CTCs) may provide an outstanding opportunity to develop such innovative methods.
Determine kinetics of CTC shedding into the circulation: Perioperative CTC detection has the potential to explain how and when CTCs are shed into the blood. Findings could explain the nature of CTCs with important impact on understanding metastatic spread and relevant clinical applications.
Since this protocol includes blood draws at multiple time points at different distances from the metastases, results could further clarify if the rarity or absence of CTCs in the peripheral blood of some mCRC patients can be explained by dilution. Comparison of patients with CRC liver to lung metastases might help explain different patterns of organ spread. Results of this study could establish CTCs as a prognostic biomarker identifying candidates who will benefit from metastasectomy or for those who are candidates for additional or palliative systemic treatments because of a high risk for later recurrence.
- Develop effective system for isolation, enumeration, enrichment and further characterization of live CTCs: One of the current issues of CTC analysis is the enrichment of those rare cells from blood. We plan to analyze perioperatively drawn blood using the flexible micro spring array (FMSA) device. The FMSA mitigates the stresses experienced by CTCs during their isolation from blood and enables viable capture. The geometric design and filtration pressures have been optimized to maximize capture efficiency, enrichment against leukocytes, and tumor cell viability. Peripheral blood as well as blood from the direct tumor environment (taken from the OR suctioning system) will be analyzed to compare the sensitivity of the FMSA and CellSearch device. Since the FMSA allows for isolation of live CTCs, they will be processed for further single cell characterization.
- Find characteristics of different CTC populations: We hypothesize that CTCs will be enriched for cancer stem cell markers as well as markers for poor prognosis and aggressive tumor growth. Our novel approach to screen and quantify a panel of biomarkers simultaneously with analysis of the CTC markers utilized by the CellSearch system to analyze of CTCs is unique. We view our assays as potential "liquid biopsies" that can screen for markers of prognosis, sensitivity to chemotherapy, response to therapy, as well as for proteins involved in proliferation, apoptosis, and immune response.
Furthermore, we plan to perform single cell analysis of gene mutations and gene expression. Next generation genomic sequencing of single CTCs may allow us to determine a genetic signature for colorectal CTCs and to identify novel biomarkers for CTC detection, disease monitoring, and therapeutic efficacy. Furthermore, the extent of heterogeneity among initially isolated CTCs, which can be compared to the primary tumor and CTCs growing in vitro, will be studied. Single CTC analysis has the potential to identify novel gene and signal transduction pathways that are activated in CTCs and to compare this genomic profile to that of the primary tumor and patient metastasis. Single cell genomic analysis in CTCs is highly innovative and will provide important information for disease monitoring as well as shed light on the underlying biology of CTCs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stage IV colorectal cancer | – | –CTCs will be drawn during liver and/or lung metastasectomy for colorectal cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 50 patients with colorectal cancer metastatic to liver and/or lungs will be enrolled. Patients must be older than 18 years. No healthy volunteers/control group will be included.
Key inclusion criteria (8 listed)
- Subjects older than 18 years will be included.
- Subjects with colorectal primary carcinomas metastatic to the liver and/or lungs who will undergo a synchronous resection of both primary tumor and liver metastases will also be enrolled.
- Subjects of all genders and ethnicities will be included.
- Subjects with the diagnosis of stage IV primary CRC will be included if metastases are limited to liver and/or lungs at the time of primary surgery.
- The histopathology of the CRC primary tumor must be documented to be adenocarcinoma.
Key exclusion criteria (4 listed)
- Subjects with the concurrent diagnosis of an active second malignancy besides basal cell carcinoma of the skin will be excluded, if there is evidence of disease burden or the patient is currently treated with chemotherapy.
- Subjects with a Hemoglobin of <8g/dl in the morning of the procedure will be excluded.
- In subjects who had needed intraoperative transfusions >4 units of RPBCs, no further blood will be drawn for CTC analysis.
- Pregnant women will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Quantity of CTCs isolated during liver and/or lung metastasectomy
Time frame: 1 year
Define in which quantity CTCs are retrievable from different blood compartments and lost blood during CRC liver and lung metastases surgery using the Veridex CellSearch system and FMSA filter device
1 secondary outcome
Overall survival
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2016.
- Results publication: PubMed 25807199Kaifi JT, Kunkel M, Das A, Harouaka RA, Dicker DT, Li G, Zhu J, Clawson GA, Yang Z, Reed MF, Gusani NJ, Kimchi ET, Staveley-O'Carroll KF, Zheng SY, El-Deiry WS. Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: a prospective trial with different detection techniques. Cancer Biol Ther. 2015;16(5):699-708. doi: 10.1080/15384047.2015.1030556.
- PubMed link to study resultsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jussuf T Kaifi, MD PhD principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stage IV Colorectal Cancer and Liver Metastases, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantity of CTCs isolated during liver and/or lung metastasectomy (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01722903, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2016.