Peritoneal Carcinomatosis Leveraging ctDNA Guided Treatment in GI Cancer Study (PERICLES Study)

Sponsor

Rutgers, The State University of New Jersey (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04929015

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

42.1

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial collects biospecimen samples to create a personalized ctDNA test to guide treatment for patients with gastrointestinal cancer with peritoneal carcinomatosis. Deoxyribonucleic acid, or DNA, is the material that carries all the information about how a living thing will work and function. Everyone is born with the same DNA in all our cells throughout our body. Sometimes, some of the cells in the body develop abnormalities in the DNA that cause those cells to grow abnormally and uncontrollably. Cancer occurs when there is abnormal and uncontrolled growth of cells. The DNA in cancer cells is therefore different from the DNA someone is born with. The Signatera ctDNA assay is a laboratory test that takes tumor (cancer) tissue and evaluates it for unique tumor DNA. This evaluation is used to create a report (otherwise known as an assay) personalized to each person's cancer. The personalized assay creates a personalized blood test to detect the level of abnormal DNA from the cancer that may be circulating in the body. Once this personalized blood assay is designed, it may be used to monitor a person's blood for the presence of ctDNA, which will indicate the presence or absence of cancer over time, even after treatment.

Condition or Disease	Intervention/Treatment	Phase
Appendix Carcinoma by AJCC V8 Stage Colorectal Carcinoma by AJCC V8 Stage Digestive System Neoplasm Esophageal Carcinoma by AJCC V8 Stage Gastric Carcinoma by AJCC V8 Stage Liver and Intrahepatic Bile Duct Carcinoma Peritoneal Carcinomatosis	Procedure: Biospecimen Collection - blood and tissue sample collection Other: Electronic Health Record Review	N/A

Detailed Description

This study is an exploratory analysis of the utility of ctDNA as a sensitive biomarker in patients with Peritoneal Carcinomatosis treated with chemotherapy, CRS and/or hyperthermic intraperitoneal chemotherapy (HIPEC).

OBJECTIVES:

To measure changes in circulating tumor deoxyribonucleic acid (ctDNA) in patients with peritoneal carcinomatosis (PC) from gastrointestinal (GI) cancers who are candidates for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC).
To determine the percentage of patients on protocol with undetectable ctDNA (clearance rate) after complete CRS.
To identify any associations between clinical staging of CRS and measurable ctDNA.
To assess changes in ctDNA levels in response to chemotherapy in patients with PC.
To guide treatment based on ctDNA response.

OUTLINE:

Patients may receive induction chemotherapy at the discretion of the treating physician for up to 6 months. Patients undergo blood sample collection for ctDNA analysis at baseline, post chemotherapy/pre-surgery, 3-4 weeks post CRS/HIPEC, then every 3 months over 2 years. Patients also undergo tissue collection before or during surgery and their medical records are reviewed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Peritoneal Carcinomatosis Leveraging ctDNA Guided Treatment in GI Cancer Study (PERICLES Study)

Actual Study Start Date :

Apr 29, 2021

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diagnostic (biospecimen collection) Patients will receive standard treatment with surgery, HIPEC, and chemotherapy as appropriate to the patient situation, extent of disease and multi-disciplinary evaluation. Patients undergo blood sample collection for ctDNA analysis at baseline, pre-surgery, post-surgery and every 3 months up to 2 years. Patients undergo tissue collection before or during surgery and their medical records are reviewed.	Procedure: Biospecimen Collection - blood and tissue sample collection The original tissue sample from each patient will be obtained at time of surgery or prior to surgery. Plasma for ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up 2 years Other: Electronic Health Record Review Medical record reviewed

Arm

Intervention/Treatment

Experimental: Diagnostic (biospecimen collection)

Patients will receive standard treatment with surgery, HIPEC, and chemotherapy as appropriate to the patient situation, extent of disease and multi-disciplinary evaluation. Patients undergo blood sample collection for ctDNA analysis at baseline, pre-surgery, post-surgery and every 3 months up to 2 years. Patients undergo tissue collection before or during surgery and their medical records are reviewed.

Procedure: Biospecimen Collection - blood and tissue sample collection

The original tissue sample from each patient will be obtained at time of surgery or prior to surgery. Plasma for ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up 2 years

Other: Electronic Health Record Review

Medical record reviewed

Outcome Measures

Primary Outcome Measures

Clearance rate of circulating tumor deoxyribonucleic acid (ctDNA) with cytoreductive surgery (CRS) [Baseline, pre-surgery, 3- 4 weeks post-surgery and then every 3 months up to 2 years after cytoreductive surgery (CRS)]
Will compare results with clinical staging of CRS (surgical staging, surgical outcomes, Peritoneal Carcinoma Index [PCI] and cytoreduction [CC] score). ctDNA clearance rate defined as the % of patients on our protocol with undetectable ctDNA. Will associate ctDNA changes with clinical response by Response Evaluation Criteria in Solid Tumors and surgical staging, surgical outcomes, PCI and CC score using standard T-testing, log-rank analysis or similar non-parametric testing.
Correlation of ctDNA clearance with activity of chemotherapy [Baseline, pre-surgery, 3-4 weekd post-surgery and then every 3 months up to 2 years after cytoreductive surgery (CRS)]
Will correlate ctDNA clearance with activity of chemotherapy in this disease pre-op and post-op

Secondary Outcome Measures

Positivity rate of ctDNA in patients with peritoneal carcinomatosis [Baseline, pre-surgery, 3-4 weeks post-surgery and then every 3 months up to 2 years after cytoreductive surgery (CRS)]
ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up to 2 years
ctDNA and its association with results of next generation sequence (NSG) analysis from original tumor tissue. [Baseline, pre-surgery, 3-4 weeks post-surgery and then every 3 months up to 2 years after cytoreductive surgery (CRS)]
ctDNA will be obtained at baseline, pre-surgery, 3-4 weeks post-surgery and then every 3 months up to 2 years. ctDNA from blood samples will be compared with the results of NSG analysis from original tumor tissue
Associations between CEA levels and ctDNA levels [Baseline, pre-surgery, 3-4 weeks post-surgery and every 3 months up to 2 years after cytoreductive surgery (CRS)]
ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up to 2 years
Associations between CA19.9 levels and ctDNA levels [Baseline, pre-surgery, 3-4 weeks post-surgery and every 3 months up to 2 years after cytoreductive surgery (CRS)]
ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up to 2 years
Associations between CA125 levels and ctDNA levels [Baseline, pre-surgery, 3-4 weeks post-surgery and every 3 months up to 2 years after cytoreductive surgery (CRS)]
ctDNA will be obtained at baseline, pre-surgery, post-surgery and every 3 months up to 2 years

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with histologically confirmed carcinoma of presumed gastrointestinal origin (gastric, esophageal, colorectal, appendiceal, hepatobiliary or peritoneal carcinomatosis of apparent GI primary) with documented diffuse peritoneal carcinomatosis, either by conventional imaging studies, positive ascitic fluid analysis, or surgical staging
Measurable or evaluable disease by cross-sectional imaging studies
Patients must be candidates for possible surgical cytoreduction (with or without HIPEC) as determined by a study surgical oncologist
Age >= 18 years
Estimated life expectancy of at least 12 months
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patients must sign informed consent
Be willing to present for medical exams, blood draws and imaging as scheduled in protocol
Be able to donate two 10 mL tubes of blood every 3 months
Women of childbearing potential will undergo routine screening evaluation for pregnancy prior to enrollment and be managed per standard of care

Exclusion Criteria:

Patients without a confirmed pathologic diagnosis of carcinoma
Second uncontrolled primary malignancy
Patients who are pregnant
Patients who cannot undergo a therapeutic surgical cytoreduction
Bone marrow transplant or other organ transplant recipient
Any unstable, serious co-existing medical conditions including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to screening
Patients with cardiovascular or pulmonary risk factors contributing to high risk for surgical complications, at the discretion of the surgeon
Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator