JCOG1920: A phase III trial of neoadjuvant Gemcitabine + Cisplatin + S-1 (GCS) vs. surgery first for resectable biliary tract cancer (NABICAT)
JCOG1920: A phase III trial of neoadjuvant Gemcitabine + Cisplatin + S-1 (GCS) vs. surgery first for resectable biliary tract cancer (NABICAT)
OKUSAKA Takuji
National Cancer Center Hospital
5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan
+81-3-3542-2511
tokusaka@ncc.go.jp
SATOMI Eriko
National Cancer Center Hospital
5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan
+81-3-3547-5293
CRL_office@ml.res.ncc.go.jp
Recruiting
Mar. 01, 2021
Mar. 19, 2021
460
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
(1) The main histological type is diagnosed as adenocarcinoma or adenosquamous carcinoma*1 by pathological diagnosis (cytology or histology) ("adenocarcinoma (details unknown)" is also eligible). Alternatively, cytology is Class IV or Class V and does not suggest a histological type other than adenocarcinoma or adenosquamous carcinoma.
*1 In the case of perihilar bile duct cancer, distal bile duct cancer, gallbladder cancer, and papillary cancer, adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma) or adenosquamous carcinoma (general rules for clinical and pathological studies on cancer of the biliary tract, 6th edition). In the case of intrahepatic bile duct cancer, adenocarcinoma or adenosquamous carcinoma of intrahepatic bile duct cancer (cholangiocellular carcinoma) (the general rules for the clinical and pathological study of primary liver cancer, 6th edition). When the pathological diagnosis is neither mucinous adenocarcinoma nor signet-ring cell carcinoma, but adenocarcinoma and there is no description as to whether it corresponds to papillary adenocarcinoma, tubular adenocarcinoma, or poorly differentiated adenocarcinoma, it is described as adenocarcinoma (details unknown) and eligible.
(2) Have been diagnosed with a biliary tract cancer (perihilar bile duct cancer, distal bile duct cancer, gallbladder cancer, papillary cancer, or intrahepatic bile duct cancer) that can be resected without macroscopically residual cancer (R0 or R1 resection) by diagnostic imaging*2.
(3) It is diagnosed that the following stages are applicable by diagnostic imaging*2. For intrahepatic bile duct cancer, use the TNM classification of the general rules for the clinical and pathological study of primary liver cancer, 6th edition, and for others, the biliary tract cancer, use that of general rules for clinical and pathological studies on cancer of the biliary tract, 6th edition). If the tumor extends to multiple regions of the perihilar bile duct, distal bile duct, gallbladder, papilla, and intrahepatic bile duct, the main occupying site of the tumor is selected as the primary tumor and use the staging of that primary tumor. If the tumor extends to multiple regions and the occupancy range is the same and the main occupancy site cannot be determined, one occupancy site most likely to be the primary site of the tumor is selected based on the imaging findings, and selected as the primary tumor and use the staging of that primary tumor.
(i) Perihilar bile duct cancer T2a or higher or N1, and M0 (Stage II-IVA)
(ii) Distal bile duct cancer T2 or higher or N1, and M0 (Stage IB-III)
(iii) Gallbladder cancer T3a or higher or N1, and M0 (Stage IIIA-IVA)
(iv) Papillary cancer T3a or higher or N1, and M0 (Stage IIA-III)
(v) Intrahepatic bile duct cancer T3 or higher or N1, and M0 (Stage III-IVA, Stage IVB (T4N1M0))
*2 Contrast-enhanced MDCT with a slice thickness of 5 mm or less is used as the diagnostic modality. However, both MDCT with a slice thickness of 5 mm or less and EUS is used as the diagnostic modality for papillary cancer.
Regarding lymph nodes, those fulfilling any of the following are diagnosed as positive for lymph node metastasis.
(a) Minimal diameter is 10 mm or more
(b) Even if the minimal diameter is less than 10 mm, it exists near the tumor and shows a contrast pattern similar to that of the tumor.
(c) Exhibiting extra-nodal invasion (fluffing)
(4) Open surgery or laparoscopic surgery is scheduled for biliary tract cancer.
(5) The scheduled surgery at the time of registration is neither the left trisectionectomy, right trisectionectomy, (extended) right hemihepatectomy and pancreaticoduodenectomy, or hepatectomy with combined resection and reconstruction of hepatic artery and portal vein. (It is permissible to select the above surgical procedure based on findings of CT performed between registration and surgery or intraoperative findings, and the protocol treatment will not be discontinued).
(6) The age of registration date is 20 years or older.
(7) Oral ingestion is possible.
(8) No watery diarrhea.
(9) Performance status (PS) is 0 or 1 according to ECOG criteria.
(10) No history of chemotherapy, radiation therapy, immunotherapy, or surgery for biliary tract cancer (treatment of jaundice *3 is acceptable).
*3 Percutaneous biliary drainage (PTBD, PTGBD, stent), endoscopic biliary drainage (ENBD, ERBD, stent), etc.
(11) No history of portal vein embolization (if portal vein embolization is required, perform it after registration).
(12) The latest test value within 14 days before registration (the same day of the week 2 weeks before registration date is acceptable) satisfies all of the followings.
(i) Number of neutrophils >= 1,500 /mm3
(ii) Hemoglobin >= 9.0 g /dL (blood transfusion must not be performed within 14 days before the blood test date used for registration)
(iii) Platelet count >= 100,000 /mm3
(iv) AST: without jaundice treatment: <=100 U /L, with jaundice treatment: <=150 U /L
(v) ALT: without jaundice treatment: <=100 U /L, with jaundice treatment: <=150 U /L
(vi) Total bilirubin: without jaundice treatment: <=2.0 mg /dL, with jaundice treatment: <=3.0 mg /dL
(vii) Serum creatinine <=1.2 mg /dL
(viii) Creatinine clearance* >= 50 mL /min
* Creatinine clearance should be 50 mL /min or more as estimated by the Cockcroft-Gault formula. If the estimated value is less than 50 mL /min, it is eligible if it is confirmed that the measured value is 50 mL /min or more.
(13) No allergy to CT contrast agent.
(14) Written consent has been obtained from the patient for participation in the study.
(1) Double biliary tract cancers (for example gallbladder cancer and bile duct cancer).
(2) Active multiple cancers (simultaneous multiple cancers and metachronous multiple cancers with a disease-free period of less than 5 years, but a history of cancer with five-year relative survival rate of 95% or more is not included in active multiple cancers, even if the disease-free period is less than 5 years, such as clinical stage I prostate cancer, clinical stage 0 or stage I laryngeal cancer which completely responded to radiotherapy, and cancers that were completely resected with the following pathological stages.
Gastric cancer "adenocarcinoma (general type)": stage 0-I, colon cancer (adenocarcinoma): stage 0-I, rectal cancer (adenocarcinoma): stage 0-I, esophageal cancer (squamous cell carcinoma, adenosquamous cell carcinoma, basaloid cell carcinoma): stage 0, breast cancer (non-invasive ductal carcinoma in situ, non-invasive lobular cancer): stage 0, breast cancer (invasive ductal carcinoma, invasive lobular cancer, Paget's disease): Stage 0-IIA, endometrial cancer (endometrioid adenocarcinoma, mucinous adenocarcinoma): stage I, prostate cancer (adenocarcinoma): stage I-II, cervical cancer (squamous cell carcinoma): stage 0, thyroid cancer (papillary carcinoma, follicular carcinoma): stage I-III, renal cancer (clear cell renal cell carcinoma, chromophobe renal cell carcinoma): stage I, other lesions equivalent to intramucosal cancer
* Staging is based on UICC-TNM, 7th edition or similar general rules for the clinical and pathological study of cancer.
(3) Infectious disease (excluding viral hepatitis) that requires systemic treatment.
(4) HIV antibody positive (HIV antibody can be untested).
(5) A fever of 38.0 degrees or higher at the time of registration.
(6) Women who are pregnant, may become pregnant, within 28 days of childbirth, or breastfeeding. Men who want to get their partner pregnant.
(7) It is judged that it is difficult to participate in the clinical trial due to complications of mental illness or psychiatric symptoms that interfere with daily life.
(8) Continuous systemic (oral or intravenous) administration of steroids or other immunosuppressive drugs.
(9) Has serious complications (heart failure, renal failure, liver failure, hemorrhagic peptic ulcer, intestinal paralysis, intestinal obstruction).
(10) Uncontrolled diabetes mellitus.
(11) Pleural effusion, ascites, or pericardial fluid (however, eligible if a small amount of bile or blood exists in the thoracic or abdominal cavity after PTBD/PTGBD treatment or PTBD/PTGBD tube replacement and it is clear that it is transient and not caused by a tumor).
(12) A history of unstable angina (angina with exacerbation or onset within the last 3 weeks) or myocardial infarction within 6 months.
(13) Uncontrolled valvular disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy.
(14) With one or more of interstitial pneumonia, pulmonary fibrosis, severe emphysema diagnosed by chest CT.
(15) Continued use of flucytosine (Ancotil(R), Domerajin(R), Alucytosine(R), Cocol(R)), phenytoin (Aleviatin(R), Hydantol(R), Phenytoin N(R)) and warfarin potassium (Alefarin(R), Samofalon(R), Warfarin(R)) is required.
(16) The total dose of cisplatin for other cancer types exceeds 180 mg /m2.
(17) Robot-assisted surgery is planned.
(18) A pathological diagnosis after cholecystectomy revealed gallbladder cancer (so-called incidental gallbladder carcinoma), and additional resection is planned.
20age old over
No limit
Both
biliary tract cancer
Group A: Surgery + adjuvant chemotherapy (S-1 therapy)
Group B: Preoperative chemotherapy (GCS therapy) + surgery + adjuvant chemotherapy (S-1 therapy)
The following GCS therapy is performed every 2 weeks, 3 cycles
Gemcitabine: 1,000 mg /m2, day 1, div, 30 min
Cisplatin: 25 mg /m2, day 1, div, 60 min
S-1: 80-120 mg /body, day 1-7, po, bid
The following adjuvant S-1 therapy is performed every 6 weeks, 4 cycles
S-1: 80-120 mg /body, day 1-28, po, bid
Overall survival
Progression free survival, Recurrence free survival of patients who underwent R0/R1 resection, Overall survival of patients who underwent R0/R1 resection, No resection rate, R0 resection rate, R0/R1 resection rate, lymph node metastasis rate, Response rate of neoadjuvant chemotherapy (Group B), Postoperative complication rate of Clavien-Dindo grade IIIa or severer, Serious adverse event rate
National Cancer Center Japan
Not applicable
Japan Agency for Medical Research and Development
Not applicable
National Cancer Center Hospital Certified Review Board
