A Phase I Study of Adjuvant Chemotherapy With GS in Biliary Tract Cancer Undergoing Resection Without Major Hepatectomy

Phase 1

Completed

• Conditions: Biliary Tract Cancer
• Interventions: Drug: Gemcitabine, S-1

• Registration Number: NCT01713387
• Lead Sponsor: Kansai Hepatobiliary Oncology Group

Brief Summary

To decide maximum tolerated dose and recommended dose of treatment using gemcitabine plus S-1 combination therapy in patients with biliary tract cancer undergoing resection without major hepatectomy

Detailed Description

Surgery currently remains the only potentially curative treatment for biliary tract cancer (BTC), and most patients develop recurrence. Therefore, effective adjuvant chemotherapy is required to increase the curability of surgery and to prolong the survival in these patients. However, to date, no standard adjuvant chemotherapy has been established, and a guideline for BTC treatment recommends that trials of adjuvant chemotherapy be carried out.

Recently, there are two reports about gemcitabine (GEM) + S-1 combination (GS)chemotherapy after surgical resection for patients with BTC. At Iwate Medical University, Takahara, et al., performed a phase I study using a regimen of repeating 28 days as 1 course. Patients received GEM on day 1 and day 15, and S-1 from day 1 to day 14. The recommended dose is 1,000 mg/m² of GEM and S-1 80 mg/m² after a pancreatoduodenectomy. The 2-year survival rate of the 34 patients that received the GS therapy was 78.6% (Cancer Chemother Pharmacol. 2012 May;69(5):1127-33). At Hiroshima University, a cycle of chemotherapy consisted of intravenous GEM of 700 mg/m² on day 1 and oral S-1 of 50 mg/m² for 7 consecutive days, followed by a 1-week break from chemotherapy (14days as 1 course). Fifty patients received GS therapy and had a significantly better 3-year survival rate (57%) compared with 53 cases of surgery alone (30%). The GS adjuvant chemotherapy was feasible and the adverse event was minimal (Ann Surg. 2009 Dec;250(6):950-6).

Thus, the regimens of these two studies were 14 or 28 days as 1 course. There was no regimen that consisted of GEM on day 1, 8 and S-1 for 14 consecutive days, followed by a 1-week break from chemotherapy (21days as 1 course), which is frequently used for unresectable BTC and pancreatic cancer.

Though a hepatectomy is frequently performed during surgery for BTC, it is unclear if the effect of the anticancer agent is affected by a hepatectomy. Because GEM is metabolized by cytidine deaminase primarily in the liver, the ability to metabolize GEM after a hepatectomy is thought to decrease. Some clinical studies demonstrated that patients who had undergone a hepatectomy could not tolerate the standard dose and schedule of GEM. For adjuvant chemotherapy with GEM, it is necessary to separately examine whether or not the patient has undergone a hepatectomy.

Considering these present conditions, we aimed to assess the safety and efficacy of GEM + S-1 combination chemotherapy (21days as 1 course regimen, which is frequently used for unresectable BTC) for BTC with the patients undergoing curative resection without a hepatectomy.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-09-18
• Study First Submitted QC: 2012-10-22
• Study First Posted: 2012-10-24
• Primary Completion: 2015-04
• Study Completion: 2017-03
• Status Verified: 2017-08
• Last Update Submitted: 2017-10-05
• Last Update Posted: 2017-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. Biliary tract cancer (BTC) with more than stage IB
2. BTC undergoing R0 or R1 resection without major hepatectomy
3. Older than 20 years old
4. PS 0 or 1
5. No treatment other than surgery
6. No dysfunction of main organs
7. Possible oral intake
8. Treatment start; after 4 weeks and within 12 weeks after surgery
9. Obtained written informed consent

Exclusion Criteria

1. Patients with resection of major hepatectomy
2. Patients with double cancers
3. Patients having severe allergy
4. Patients with severe organ dysfunction
5. Patients with active infectious disease
6. Pregnancy
7. Patients with severe psychological disease
8. Patients seem inadequate for this study by investigators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
gemcitabine , S-1	Gemcitabine, S-1	Level-2 Gem 800mg/msq, S-1 50mg/msq Level-1 Gem 800mg/msq, S-1 65mg/msq Level 1 Gem 1000mg/msq, S-1 65mg/msq Level 2 Gem 800mg/msq, S-1 80mg/msq

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose	6 weeks	To establish the maximum tolerated dose of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy

Secondary Outcome Measures

Name	Time	Method
Number of Participants with dose limiting toxicity	At the end of adjuvant chemotherapy (6 months)	Dose limiting toxicity is defined as follows; 1. Grade 4 neutropenia, thrombocytopenia; 2. Grade 3 or 4 febrile neutropenia; 3. Grade 3 or 4 non-hematological adverse events unless unresponsive to treatment; 4. Any adverse events resulting in interruption of dosing on day 8 in both the two courses; 5. Any adverse events resulting in dose modification or delay of longer than 2 weeks

Trial Locations

Locations (1)

Kansai Medical University; 🇯🇵 Hirakata, Osaka, Japan