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Phase II Randomized Trial of SLOG vs GC in Locally Advanced or Metastatic Biliary Tract Cancer

Primary Purpose

Biliary Tract Neoplasms

Status

Active

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

Tegafur

Leucovorin

Oxaliplatin

Gemcitabine

Cisplatin

About this trial

This is an interventional treatment trial for Biliary Tract Neoplasms focused on measuring SLOG

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Taiwan Cooperative Oncology Group, National Health Research Institutes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SLOG regimen

GC regimen

Arm Description

Arm 1 interventions : SLOG regimen: treatment for every 14 days as one cycle Tegafur (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

Arm 2 interventions : GC regimen: treatment for 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

Outcomes

Primary Outcome Measures

6-month progression-free survival rate

Tumor response will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)Guidelines version 1.1.

Secondary Outcome Measures

tumor response

Efficacy evaluations: objective tumor response according to RECIST 1.1

Overall survival

Overall survival: defined as the time from the date of first study treatment to the date of patient death, due to any cause, or to the last date the patient was known to be alive. The primary analysis population for the overall survival will be per-protocol population. The endpoint will also be analyzed in the intent-to-treat population. Kaplan-Meier estimates will be calculated for the overall survival.

Disease control rate (Objective response rate (ORR) + stable disease ≧ 12 weeks)

Efficacy evaluations: objective tumor response according to RECIST 1.1

Safety profile

Adverse events (AEs) will be evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4 (CTCAE v4).All required pre-treatment and interim data should be available and the physician must have made a designation as to response if a re-evaluation has been performed and the grade of toxicity if any has occurred。

Biomarker study

evaluated for biomarkers, including inflammatory cytokine (TGF-β, hepatocyte growth factor (HGF), interleukin (IL)-6, IL-8, IL-1, CXCL-1, Chemokine (C-X-C motif) ligand 3(CXCL-3), and stromal-derived factor (SDF)...etc). Tumor DNA will be extracted from formalin-fixed paraffin-embedded(FFPE) slides for p53, CDKN2A and AT-rich interactive domain-containing protein 1A (ARID1A) mutation which were reported to be correlated with chemotherapy resistance

Full Information

NCT ID

NCT03406299

First Posted

January 7, 2018

Last Updated

April 9, 2023

Sponsor

National Health Research Institutes, Taiwan

1. Study Identification

Unique Protocol Identification Number

NCT03406299

Brief Title

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 19, 2018 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Health Research Institutes, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Biliary Tract Neoplasms

Keywords

SLOG

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

92 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SLOG regimen

Arm Type

Experimental

Arm Description

Arm Title

GC regimen

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tegafur

Other Intervention Name(s)

S-1

Intervention Description

Tegafur(S-1) 35 mg/m2/b.i.d., day 1 - 7 (maximum dose: 120 mg/day)

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Other Intervention Name(s)

Folinic acid

Intervention Description

Leucovorin 30 mg/b.i.d., day 1-7

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

oxalic

Intervention Description

Oxaliplatin 85 mg/m2 in 250 mL of 5% Glucose, given as 2-hour intra- venous infusion, day 1

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemmis

Intervention Description

Gemcitabine 800 mg/m2 in 250 mL of normal saline, given as fixed dose-rate (, 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. in SLOG arm. Gemcitabine 1000 mg/m2 in 100 mL of normal saline, IV drip for 30 mins on D1 and D8 ，in GC arm

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin 25 mg/m2 in 250ml of normal saline, IV drip for 2 hours on D1 and D8

Primary Outcome Measure Information:

Title

6-month progression-free survival rate

Description

Tumor response will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)Guidelines version 1.1.

Time Frame

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 Outcome Measure Information:

Title

tumor response

Description

Efficacy evaluations: objective tumor response according to RECIST 1.1

Time Frame

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 .

Title

Overall survival

Description

Time Frame

Overall survival will be assessed. From date of registration until the date of death, assessed up to 60 months.

Title

Disease control rate (Objective response rate (ORR) + stable disease ≧ 12 weeks)

Description

Efficacy evaluations: objective tumor response according to RECIST 1.1

Time Frame

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 .

Title

Safety profile

Description

Time Frame

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 .

Title

Biomarker study

Description

Time Frame

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 .

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li-Tzong Cheng, PHD

Organizational Affiliation

National Health Research Institute, Cancer Research

Official's Role

Study Chair

Facility Information:

Facility Name

Taiwan Cooperative Oncology Group, National Health Research Institutes

City

Taipei

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase II Randomized Trial of SLOG vs GC in Locally Advanced or Metastatic Biliary Tract Cancer

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