mFOLFIRINOX Plus Radiotherapy to Patients With CA19-9-normal Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of mFOLFIRINOX plus radiotherapy to Patients with CA19-9-normal Advanced Pancreatic Cancer.

Detailed Description
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Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy with a 5-year survival less than 10%. Approximately 80% of patients with pancreatic cancer are diagnosed at an advanced stage. Chemotherapy is one of the major treatments for advanced pancreatic cancer. In 2011, the PRODIGE trial has shown that oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) was associated with a survival advantage but had increased toxicity. Carbohydrate antigen 19-9 (CA19-9) is the most widely used biomarker in pancreatic cancer. Circulating CA19-9 levels are positively correlated with tumor burden and stage in pancreatic cancer with a diagnostic sensitivity of approximately 80%, suggesting that approximately 20% of patients have normal CA19-9 levels. It is well recognized that Lewis (-) individuals, constituting approximately 10% of the population, have low or no secretion of CA19-9 due to the lack of critical enzyme involved in CA19-9 biosynthesis. Thus, approximately 10% of patients with pancreatic cancer have normal CA19-9 levels regardless of tumor stage. Our previously retrospective study has shown that CA19-9-normal advanced pancreatic cancer may be more sensitive to chemotherapy combined with radiotherapy. The purpose of this study is to evaluate the efficacy of mFOLFIRINOX plus radiotherapy to patients with CA19-9-normal advanced pancreatic cancer. Progression-free survival (PFS), objective response rate (ORR), overall survival (OS) and disease control rate (DCR) are measured every four weeks.

Official Title
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mFOLFIRINOX Plus Radiotherapy to Patients With CA19-9-normal Advanced Pancreatic Cancer

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Combination Product: mFOLFIRINOX plus radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document. Age ≥ 18 years and ≤ 80 years. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Histologically or cytologically confirmed advanced pancreas adenocarcinoma. Patients who have not received any form of anti-tumor therapy. Baseline serum CA19-9 ≤ 37 U/mL and Lewis antigen positive genotype. Presence of at least of one measurable lesion in agreement to RECIST criteria. The expected survival ≥ 3 months. Adequate organ performance based on laboratory blood tests. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Exclusion Criteria: Pregnant or nursing women. Patients who have received any form of anti-tumor therapy. Baseline serum CA19-9 ≥ 37 U/mL, or Lewis antigen negative genotype. The diagnosis was confirmed by pathology as non-adenocarcinoma of pancreas. Inflammation of the digestive tract, including pancreatitis, cholecystitis, cholangitis, etc. Severe and uncontrollable accompanying diseases that may affect protocol compliance or interfere with the interpretation of results. Renal insufficiency or dialysis Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment. Patients who are allergic to oxaplatin or other chemotherapy drugs. Patients who are unwilling or unable to comply with study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mFOLFIRINOX plus radiotherapy<br>Patients with advanced pancreatic adenocarcinoma will receive a modified FOLFIRINOX regimen (oxaliplatin [70 mg per square meter of body surface area], irinotecan [130 mg per square meter], leucovorin [200 mg per square meter], and fluorouracil [2000 mg per square meter] every 2 weeks). Four-week chemotherapy is considered as a cycle. Patients will be recommended to receive Intensity-Modulated Radiation Therapy (IMRT) after about 4 6 cycles of chemotherapy. The following treatment after radiotherapy will be applied according to the newest edition of National Comprehensive Cancer Network (NCCN) guideline. | Combination Product: mFOLFIRINOX plus radiotherapy<br>* Patients with advanced pancreatic adenocarcinoma will receive a modified FOLFIRINOX regimen (oxaliplatin [70 mg per square meter of body surface area], irinotecan [130 mg per square meter], leucovorin [200 mg per square meter], and fluorouracil [2000 mg per square meter] every 2 weeks). Four-week chemotherapy is considered as a cycle. Patients will be recommended to receive Intensity-Modulated Radiation Therapy (IMRT) after about 4 6 cycles of chemotherapy. The following treatment after radiotherapy will be applied according to the newest edition of National Comprehensive Cancer Network (NCCN) guideline.<br>* Other names: mFOLFIRINOX plus IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival，OS | OS of subjects from recruiting to the time of death from any cause | At the end of Cycle 1 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival, PFS | PFS of subjects from recruiting to the time of disease progression | At the end of Cycle 1 (each cycle is 21 days) | 
| objective response rate (ORR) | CR + PR | At the end of Cycle 1 (each cycle is 21 days) | 
| disease control rate (DCR) | CR + PR + SD | At the end of Cycle 1 (each cycle is 21 days) |