Multicenter Study of Circulating Tumor DNA in Patients With Pancreatic Cancer Using a Personalized Panel

Study Overview
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Brief Summary
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This is a multicenter, prospective, observational study to evaluate the utility of the Invitae Personalized Cancer MonitoringTM assay for patients with resectable and unresectable pancreatic cancer. Using tumor tissue, a personalized blood test (the Invitae Personalized Cancer MonitoringTM test) will be developed that can be used for repeated monitoring to assess for the presence or absence of circulating tumor DNA (ctDNA). The presence of residual cancer cells after treatment is known as molecular residual disease (MRD) and the detection of ctDNA can provide evidence of the presence of MRD. Participants in this study will have their blood drawn at various time points throughout their cancer treatment to test for ctDNA and monitoring with the Invitae Personalized Cancer MonitoringTM test will continue until disease progression or the duration of the study.

Detailed Description
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This is a multi-site, prospective, observational trial in Japan of 150 pts with resectable (50) and unresectable (100) PC. The main eligibility criteria are histopathologically diagnosed as adenocarcinoma, no prior treatment for PC, scheduled to undergo surgery for resectable PC or receive systemic therapy for unresectable PC. In resectable PC cohort, blood samples will be collected before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after surgery, and imaging study will be performed before surgery, and at 3, 6, 9, 12, 18, and 24 months after surgery. In the unresectable PC cohort, blood samples will be collected before treatment and at 4, 8, 12, 16, 24, 32, 40, and 48 weeks on treatment, and imaging study will be performed before treatment and every 8 weeks on treatment until 48 weeks. Primary endpoint in the resectable PC cohort is success rate of creating personalized panel using tumor tissue obtained by EUS-FNA/FNB, and that in unresectable PC cohort is rate of concordance of KRAS mutations between tumor tissue and blood samples. Key secondary endpoints in resectable PC cohort are rate of ctDNA positivity for each cancer stage before neoadjuvant chemotherapy and 4 weeks after surgery, and that in unresectable PC cohort is pretreatment ctDNA detection rate for each disease stage.

Official Title
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Multicenter Study of Circulating Tumor DNA in Patients With Pancreatic Cancer Using a Personalized Panel

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A. Unresectable Pancreatic Cancer: At least 20 years of age at the time of consent Histopathologically confirmed adenocarcinoma and diagnosed as having ① or ② described below within 60 days prior to enrollment Clinical Stage Ⅲ (T1-3N2M0, T4 anyNM0) Clinical Stage Ⅳ (anyTanyNM1) Scheduled to receive systemic chemotherapy for unresectable pancreatic cancer. No prior treatment for pancreatic cancer Willing to provide blood and tissue samples in accordance with the research protocol. Adequate tissue samples are available Written informed consent for participating in this study B. Resectable Pancreatic Cancer: At least 20 years of age at the time of consent. Tissue sample collected by EUS-FNA/FNB and histopathologically diagnosed as having adenocarcinoma. Diagnosed as having cancer meet any one of a to d below within 60 days prior to enrollment cStage IA (T1 N0 M0) cStage IB (T2 N0 M0) cStage IIA (T3 N0 M0) cStage IIB (T1-3 N1 M0) Scheduled to undergo surgery for resectable pancreatic cancer. No history of prior treatment for pancreatic cancer. Willing to submit blood and tissue samples in accordance with the research protocol. Adequate tissue samples are available Written informed consent for participating in this study Exclusion Criteria: Common exclusion criteria for both the unresectable and resectable pancreatic cancer patient cohorts: Synchronous double/multiple cancer or metachronous double/multiple cancer with progression free period of 2 years or shorter. Women who are pregnant or planning to become pregnant. Judged by the investigator as being unsuitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Unresectable Pancreatic Cancer<br> | Other: No intervention<br>* There is no intervention associated with this observational study.<br>|
| Resectable Pancreatic Cancer<br> | Other: No intervention<br>* There is no intervention associated with this observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort of patients with unresectable pancreatic cancer; Rate of concordance of KRAS mutations between tumor tissue and blood samples Primary endpoint | Compare the presence or absence of KRAS mutations in the tumor tissue to the presence or absence of KRAS mutations in the blood for cases in which KRAS is included in the patient specific panel | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Success rate of WES assays and selections of personalized genes using tumor tissue specimens obtained by EUS-FNA/FNB | Calculate the proportion of patients with resectable pancreatic cancer who are able to successfully have a custom ctDNA panel created with the EUS-FNA/FNB tissue provided | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort of patients with unresectable pancreatic cancer; Pretreatment ctDNA detection rate for each disease stage (stage III and stage IV) | Calculate the proportion of patients with stage III and stage IV with a positive Invitae Personalized Cancer Monitoring test prior to receiving any treatment. | 3 years | 
| Cohort of patients with unresectable pancreatic cancer; Association of pretreatment ctDNA detection rate and the treatment efficacy | Compare the proportion of patients who have a positive versus negative Invitae Personalized Cancer Monitoring test prior to treatment with treatment efficacy as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria after the start of 1st line chemotherapy. | 3 years | 
| Cohort of patients with unresectable pancreatic cancer; Association of pretreatment serum marker levels (CA19-9) and treatment efficacy | Compare CA19-9 levels in the blood as measured by units per millimeter (u/mL) prior to receiving any treatment to treatment efficacy as measured by RECIST criteria | 3 years | 
| Cohort of patients with unresectable pancreatic cancer; Association of pretreatment serum marker levels (CEA) and treatment efficacy | Compare CEA levels in the blood as measured by nanograms per milliliter of blood (ng/mL) prior to receiving any treatment to treatment efficacy as measured by RECIST criteria | 3 years | 
| Cohort of patients with unresectable pancreatic cancer; Association of ctDNA levels and treatment efficacy | Compare ctDNA levels as measured by ctDNA fraction in the Invitae Personalized Cancer Monitoring test prior to receiving any treatment to treatment efficacy as measured by RECIST criteria | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Rate of ctDNA positivity for each cancer stage (stage IA-stage IIB) before neoadjuvant chemotherapy (NAC) and 4 weeks after surgery | Calculate the proportion of patients by each cancer stage (IA-stage IIB) with a positive Invitae Personalized Cancer MonitoringTM test before the start of neoadjuvant therapy and at the blood draw 4 weeks after surgery. | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Association of preoperative ctDNA before NAC and overall survival | Compare overall survival between patients who have a positive versus negative Invitae Personalized Cancer MonitoringTM test prior to neoadjuvant treatment | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Association of postoperative ctDNA before adjuvant chemotherapy (AC) and overall survival | Compare overall survival between patients who have a positive versus negative Invitae Personalized Cancer MonitoringTM test after surgery | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Proportion of ctDNA positivity at the time of recurrence detected by diagnostic imaging | Calculate the proportion of patients with a positive Invitae Personalized Cancer Monitoring test at the time of clinical recurrence as detected by imaging scans | 3 years | 
| Cohort of patients with resectable pancreatic cancer, Association of CA-19-9 levels before neoadjuvant chemotherapy and before adjuvant chemotherapy with recurrence free survival | Compare CA19-9 levels as measured by units per millimeter (u/mL) before neoadjuvant chemotherapy and before adjuvant chemotherapy to recurrence free survival | 3 years | 
| Cohort of patients with resectable pancreatic cancer, association of CEA levels before neoadjuvant chemotherapy and before adjuvant chemotherapy with recurrence free survival | Compare CEA levels as measured by nanograms per milliliter of blood (ng/mL) before neoadjuvant chemotherapy and before adjuvant chemotherapy to recurrence free survival | 3 years | 
| Cohort of patients with resectable pancreatic cancer, association of ctDNA levels before neoadjuvant chemotherapy and before adjuvant chemotherapy with recurrence free survival | Compare ctDNA levels as measured by ctDNA fraction in the Invitae Personalized Cancer Monitoring test before neoadjuvant chemotherapy and before adjuvant chemotherapy to recurrence free survival | 3 years | 
| Cohort of patients with resectable pancreatic cancer; Differences in OS and PFS between the patients in whom the personalized panel can be created and those in whom it cannot be created | Compare the ability to generate a personalized ctDNA panel with disease free and overall survival | 3 years | 
| Cohort of patients with resectable pancreatic cancer; to investigate the lead time of ctDNA detection of recurrence before detection of recurrence via imaging methods | Calculate the lead time as measured by months between a positive Invitae Personalized Cancer Monitoring test and positive imaging findings by either CT or MRI | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circulating tumor DNA, Molecular Residual Disease, Pancreatic Cancer