境界型切除可能および局所進行膵臓腺癌に対するネオアジュバント化学療法

• Gemcitabine (1000 mg/m2 weekly, on day 1,8 and 15 OR 1000 mg/m2 weekly, on day 1 and 15 over 30 minutes after nab-paclitaxel infusion.

• nab-Paclitaxel (125 mg/m2 weekly, on days 1,8, and 15 OR on days 1 and 15 as a 30-40 minute infusion administered first) for one month and then transition to mFOLFIRNIOX for one month.

  • 1 Cycle = 4 weeks: Day 1,8,15 in a 28 day cycle; 3 consecutive weeks (weeks 1, 2, and 3) of chemotherapy with 1 week off, OR
  • 1 Cycle = 4 weeks: Day 1, 15 in a 28 day cycle; Every other week (weeks 1 and 3) of chemotherapy with 2nd and 4th week off

• mFOLFIRINOX: Oxaliplatin, 85 mg/m² IV once every two weeks over 2 hours on Day 1; Irinotecan, 150 mg/m² IV once every two weeks over 90 minutes on Day 1; 5-FU, 2,400 mg/m² IV once every two weeks over 46-48 hours administered via infusion; Leucovorin, 400 mg/m2 IV every two weeks over 90 minutes on Day 1.

  • 1 Cycle = 4 weeks, administration on Day 1 and Day 15 of each mFOLIRINOX cycle

The intervention will be administered on an outpatient basis. The patients on this study will begin treatment with GA for one month and then transition to mFFX for one month.

The patient will come off of the sequence study intervention if the imaging after the 2nd month shows unequivocal progression. After four months of sequential neoadjuvant therapy the patient will come off study and can proceed to surgery, radiation, or extended course of chemotherapy as determined by the multidisciplinary tumor board consensus or the treating physician.

The intervention will be administered on an outpatient basis. The patients on this study will begin treatment with GA for one month and then transition to mFFX for one month.

The patient will come off of the sequence study intervention if the imaging after the 2nd month shows unequivocal progression. After four months of sequential neoadjuvant therapy the patient will come off study and can proceed to surgery, radiation, or extended course of chemotherapy as determined by the multidisciplinary tumor board consensus or the treating physician.

CT imaging of chest abdomen and pelvis will be performed every 8 weeks. MRI may be used.

The intervention will be administered on an outpatient basis. The patients on this study will begin treatment with GA for one month and then transition to mFFX for one month.

The patient will come off of the sequence study intervention if the imaging after the 2nd month shows unequivocal progression. After four months of sequential neoadjuvant therapy the patient will come off study and can proceed to surgery, radiation, or extended course of chemotherapy as determined by the multidisciplinary tumor board consensus or the treating physician.

The R0 resection is assessed only in patients who undergo surgery. R0 resection is a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. Participants are considered to be evaluable if they receive at least one sequence of treatments with GA and mFFX (1 cycle GA followed by 1 cycle of m FFX). Primary analysis for each cohort will calculate the R0 resection rate with one-sided 95% confidence interval.

The R0 resection is assessed only in patients who undergo surgery. R0 resection is a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. Participants are considered to be evaluable if they receive at least one sequence of treatments with GA and mFFX (1 cycle GA followed by 1 cycle of m FFX). Primary analysis for each cohort will calculate the R0 resection rate with one-sided 95% confidence interval.

The incidence of treatment-emergent toxicities/adverse events (AEs) and Serious Adverse Events (SAEs) in terms categorized and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5). Incidence tables will be generated to summarize incidence of patients reporting at least one episode of each specific adverse event, incidence of adverse events causing withdrawals and incidence of serious adverse events, separated by cohort.

The number of participants to complete 4 cycles of sequential chemotherapy.

Progression free survival (PFS) is defined from the day of study treatment initiation until progression according to RECIST v 1.1 guidelines (Progression: One or more of the following must occur: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed [over baseline if no decrease during therapy] using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of the treating physician) or death of any cause, whichever occurs first, as measured throughout the study. Stratified Kaplan-Meier curves will be constructed to assess PFS with estimated 6-month and median times with 95% confidence intervals.

Overall survival (OS) is defined from the time of study treatment initiation until death of any cause. Stratified Kaplan-Meier curves will be constructed to assess OS with estimated 6-month and median times with 95% confidence intervals.

Tumor response based defined as the proportion of patients who achieve complete response or partial response based on RECISTv1.1 criteria. These will be evaluated according to the RECISTv1.1 criteria using a summarized count/percent with one-sided 95% confidence interval for each cohort:

The RECIST v1.1 definitions include:

Complete Response (CR): The disappearance of all target lesions.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

Disease control is defined as the proportion of patients with a disease control rate (complete + partial response + stable disease) based on RECISTv1.1 criteria using a summarized count/percent with one-sided 95% confidence interval for each cohort.

Complete Response (CR): Complete disappearance of all target and non-target lesions (with the exception of lymph nodes mentioned below). No new lesions. No disease related symptoms.

Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions.

Stable: Does not qualify for CR, PR, Progression or Symptomatic Deterioration. All target measurable lesions must be assessed using the same techniques as baseline.