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

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.

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.

Eligibility Criteria:
Inclusion Criteria:

A. Unresectable Pancreatic Cancer:

1. At least 20 years of age at the time of consent
2. 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)
3. Scheduled to receive systemic chemotherapy for unresectable pancreatic cancer.
4. No prior treatment for pancreatic cancer
5. Willing to provide blood and tissue samples in accordance with the research protocol.
6. Adequate tissue samples are available
7. Written informed consent for participating in this study

B. Resectable Pancreatic Cancer:

1. At least 20 years of age at the time of consent.
2. Tissue sample collected by EUS-FNA/FNB and histopathologically diagnosed as having adenocarcinoma.
3. Diagnosed as having cancer meet any one of a to d below within 60 days prior to enrollment

   1. cStage IA (T1 N0 M0)
   2. cStage IB (T2 N0 M0)
   3. cStage IIA (T3 N0 M0)
   4. cStage IIB (T1-3 N1 M0)
4. Scheduled to undergo surgery for resectable pancreatic cancer.
5. No history of prior treatment for pancreatic cancer.
6. Willing to submit blood and tissue samples in accordance with the research protocol.
7. Adequate tissue samples are available
8. Written informed consent for participating in this study

Exclusion Criteria:

Common exclusion criteria for both the unresectable and resectable pancreatic cancer patient cohorts:

1. Synchronous double/multiple cancer or metachronous double/multiple cancer with progression free period of 2 years or shorter.
2. Women who are pregnant or planning to become pregnant.
3. Judged by the investigator as being unsuitable for participation in the study.