GABARNANCE TRIAL

Randomized phase II/III study of gemcitabine and nab-paclitaxel therapy versus S-1 and concurrent radiotherapy as neoadjuvant treatment for Borderline resectable pancreatic cancer

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Overview

Randomized phase II/III study of gemcitabine and nab-paclitaxel therapy versus S-1 and concurrent radiotherapy as neoadjuvant treatment for Borderline resectable pancreatic cancer - GABARNANCE Trial

Study Overview

GABARNANCE Trial

Objectives

Preopeartive adjuvant therapies gemecitabine + nab-paclitaxel cobmbination therapy (hereinafter GEM + nab-PTX therapy) and radiotherapy combined with S-1, which are deemed the standard therapies for borderline resectable pancreatic cancer (hereinafter BR pancreatic cancer), will be verified for their efficacy and safety in a phase II/III randomized controlled study.

Phase II part

Primary endpoint:

R0 resection rate in each group (not compared between groups)

Secondary endpoint:

Incidence of adverse events

Phase III part

Primary endpoint:

Overall survival

Secondary endpoints:

Progression-free survival, R0 resection rate, 2-year survival rate, imaging response rate, histological response rate, incidence of adverse events and protocol treatment compliance (completion rates of the preoperative treatments and the entire protocol treatment)

Inclusion Criteria

  1. Central Imaging Assessment by Central Imaging Diagnosis System has confirmed that the BR pancreatic cancer meets the definition of the study.
  2. Histopathology or cytology has confirmed adenocarcinoma or adenosquamous carcinoma (based on General Rules for the Study of Pancreatic Cancer 7th edition).
  3. Diagnostic imaging has found no remote metastasis corresponding to M1 in General Rules for the Study of Pancreatic Cancer 7th edition.
  4. Age is not under 20 or over 79 years at the time of enrollment
  5. Performance Status (ECOG) is 0 or 1.
  6. No history of radiotherapy in the abdomen
  7. No history of chemotherapy within the past 3 years
  8. Naive (no treatment history for pancreatic cancer)
  9. The radiotherapist considers that the primary foci and lymph node metastases can all be included in the field size of 10 cm x 10 cm on thoraco-abdominal CT (including PET positive lymph nodes if PET has been performed).
  10. Capable of oral intake
  11. No peripheral sensory neuropathy or peripheral motor neuropathy
  12. Appropriate drainage is performed in cases with obstructive jaundice.
  13. No gastrointestinal invasion extruding to the lumen in imaging findings such as CT or history of associated bleeding
  14. The latest laboratory results within 7 days before the enrollment meets all items below (those taken on the same day of the week 7 days before the enrollment is permissible).
    1. WBC ≥3,000/mm3
    2. Hemoglobin ≥9.0 g/dL (no transfusion within 7 days before the enrollment)
    3. Platelet count ≥10×104/mm3
    4. Albumin ≥3.0 g/dL
    5. Total bilirubin ≤2.0 mg/dL (with or without biliary drainage)
    6. AST ≤100 U/L (with or without biliary drainage)
    7. ALT ≤100 U/L (with or without biliary drainage)
    8. Serum creatinine ≤1.2 mg/dL
    9. Creatinine clearance ≥50 mL/min P
  15. The patient has submitted written consent to participation in the study.

Definition of borderline resectable pancreatic cancer

Pancreatic cancer having no remote metastasis and meeting one or more of the following (1) to (4) without the condition for unresectable pancreatic cancer:

  1. Invasion of the portal/superior mesenteric vein in ≥180 degrees not beyond the inferior border of duodenum
    • Portal/superior mesenteric venous obstruction capable of reconstruction is considered to be borderline resectable pancreatic cancer
    • Portal/superior mesenteric venous obstruction due to tumor thrombi is considered to be unresectable pancreatic cancer
  2. A tumor contacting the superior mesenteric artery in a range <180 degrees without deformation or stenosis
    • A lesion evolving in a caudal direction from the second jejunal artery is considered to be unresectable pancreatic cancer.
  3. Cancer in the head of the pancreas contacting the common hepatic artery in a range <180 degrees without deformation, stenosis or contact with the proper hepatic artery or celiac artery
  4. Cancer in the body or tail of the pancreas contacting the celiac artery, common hepatic artery or both in a range <180 degrees without deformation or stenosis
    • A lesion contacting or invading the aorta is considered to be unresectable pancreatic cancer.

Protocol treatment

1) Preoperative adjuvant therapy

Group A: GEM + nab-PTX therapy

GEM: 1000 mg/m2
nab-PTX: 125 mg/m2
Administered 6 times in total

Group B: Radiotherapy combined with S-1

S-1: 80 mg/mP2P/day
Radiotherapy: 50.4Gy/28 fraction

2) Surgical therapy

Surgical resection will be performed 15 days after the completion of the preoperative adjuvant therapy or later within 56 days in Group A or Group B.

3）Postoperative adjuvant chemotherapy

  • The postoperative adjuvant chemotherapy will start between Day 14 (Week 2) and Day 84 (Week 12) after the operation.
  • Postoperative chemotherapy is basically performed as 4 courses of S-1 single therapy (80 mg/m2/day for 4 weeks followed by 2-week drug withdrawal). Postoperative adjuvant chemotherapy S-1 will be performed over 154 days.

Estimated Enrollment and study period

Estimated Enrollment: 110 cases
Enrollment period: 5 years
Follow-up period: 2.5 years
Total study period: 7.5 years