Clinical trial NCT03406299: Phase II Randomized Trial of SLOG vs GC in Locally Advanced or Metastatic Biliary Tract Cancer
Official title: Phase II Randomized Trial of S-1, Leucovorin, Oxaliplatin and Gemcitabine (SLOG) vs Gemcitabine and Cisplatin (GC) in Locally Advanced or Metastatic Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Biliary Tract Neoplasms
Keywords: SLOG
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
First posted: 2018-01-23
Enrollment: 92
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the following items in patients with locally advanced and metastatic biliary tract cancer receiving SLOG or GC treatment, Primary objective: 6-month progression-free survival rate

Secondary objectives:

Objective response rate Disease control rate (Objective response rate (ORR) + stable disease ≧ 12 weeks) Progression-free Survival Overall survival Safety profile Biomarker study

Detailed description: To evaluate the following items in patients with locally advanced and metastatic biliary tract cancer receiving SLOG or GC treatment, Primary objective: 6-month progression-free survival rate Secondary objectives: Objective response rate、Disease control rate (Objective response rate (ORR) + stable disease ≧ 12 weeks)、Progression-free Survival 、Overall survival 、 Safety profile、Biomarker study This is a randomized, open-labeled, two-arm, multi-center, phase II clinical study.

Arm 1: SLOG regimen: every 14 days as one cycle S-1 35 mg/m2/b.i.d., day 1 - 7 (maximum dose: 120 mg/day) Leucovorin 30 mg/b.i.d., day 1-7; Oxaliplatin 85 mg/m2 in 250 mL of 5% Glucose, given as 2-hour intra- venous infusion, day 1; Gemcitabine 800 mg/m2 in 250 mL of normal saline, given as fixed dose-rate (FDR, 10 mg/m2/min) infusion, day 1; After the administration of gemcitabine, the infusion line should be flushed with 20 ml of normal saline and then 50 ml of 5% glucose solution before the administration of oxaliplatin.

Arm2: GC regimen: every 21 days as one cycle Gemcitabine 1000 mg/m2 in 100 mL of normal saline, IV drip for 30 mins on D1 and D8 Cisplatin 25 mg/m2 in 250ml of normal saline, IV drip for 2 hours on D1 and D8

Treatment will be stopped in case of progressive disease, unacceptable toxicity, patients' refusal or death.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed, advanced or metastatic biliary tract carcinoma (including intrahepatic bile duct, hilum bile duct, extrahepatic bile duct and gallbladder), except ampulla vater cancer or combined hepatocholangiocarcinoma.
* presence of at least one measurable tumor lesion which is defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) ≥20 mm using conventional techniques or ≥10 mm with spiral CT and MRI; measurable lymph nodes must be≥15 mm in the short axis.
* Patients must have no history of prior chemotherapy for Biliary Tract Cancer, except those delivered as adjuvant setting that completed at least 6 months before documentation of recurrence by imaging study.
* Patients with prior radiotherapy are eligible if the irradiated area does not involve the only source of measurable / evaluable disease.
* Patients' baseline Eastern Cooperative Oncology Group (ECOG)performance status must be less than or equal 1.
* Patients' life expectancy must be 12 weeks or greater.
* Patients' age must be more than or equal 20 years old.
* Patients must have adequate bone marrow function, defined as white blood cell (WBC) count ≥3,500/ul, absolute neutrophil count (ANC) 1,500/ul, and platelet count ≥100,000/ul.
* Patients must have adequate liver function and adequate renal function, defined as the following: serum alanine (ALT) 3 times upper normal limit, serum total bilirubin level less than or equal 2.0 mg/dL, and creatinine clearance rate (CCr) ≥ 60 mL/min ((based upon 24-hour urine collection or calculated by Cockcroft-Gault formula).
* Patients with biliary obstruction and adequate drainage procedures before enrollment are eligible.
* Patients must agree to have indwelling venous catheter implanted.
* Women or men of reproductive potential should agree to use an effective contraceptive method.
* All patients must be informed of the investigational nature of this study and must sign and give written informed consent.

Exclusion Criteria:

* Patients who have major abdominal surgery, radiotherapy or other investigating agents within 4 weeks are not eligible. Patients who have palliative radiotherapy for bony metastasis will be eligible 2 weeks after the completion of radiotherapy.
* Patients with central nervous system metastasis
* Patients with active infection
* Pregnant or breast-nursing women
* Patients with active cardiopulmonary disease or history of ischemic heart disease
* Patients who have peripheral neuropathy \> Grade I of any etiology, presence of grade 2 or above ascites or pleural effusion, or ≥ grade 2 of diarrhea.
* Patients who have serious concomitant systemic disorders incompatible with the study, i.e. poorly controlled diabetes mellitus, auto-immune disorders, cirrhosis of the liver, and the rest will be at the discretion of in-charged investigator.
* Patients who have other prior or concurrent malignancy except for adequately treated in situ carcinoma of cervix or adequately treated basal cell carcinoma of skin, or any malignancy remains disease-free for 3 or more years after initial curative treatment
* Patients who are under biologic treatment for their malignancy

Primary outcomes:
measure: 6-month progression-free survival rate
timeFrame: From date of registration to the date of disease progression or date of death from any cause, whichever came first, assessed up to 26 weeks .
Secondary outcomes:
measure: tumor response
timeFrame: From date of registration to the date of disease progression or date of death from any cause, whichever came first, assessed up to 26 weeks .
measure: Overall survival
timeFrame: Overall survival will be assessed. From date of registration until the date of death, assessed up to 60 months.
measure: Disease control rate (Objective response rate (ORR) + stable disease ≧ 12 weeks)
timeFrame: From date of registration to the date of disease progression or date of death from any cause, whichever came first, assessed up to 26 weeks .
measure: Safety profile
timeFrame: From date of registration to the date of disease progression or date of death from any cause, whichever came first, assessed up to 26 weeks .
measure: Biomarker study
timeFrame: From date of registration to the date of disease progression or date of death from any cause or date of unacceptable toxicity or date of patient's refusal , whichever came first, assessed up to 26 weeks .
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taiwan Cooperative Oncology Group, National Health Research Institutes
Study officials:
affiliation: National Health Research Institute, Cancer Research
name: Li-Tzong Cheng, PHD
role: STUDY_CHAIR
References: