Back to resultsA Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer
Primary Purpose
Rectal Cancer
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
5-FU with leucovorin
TS-1 with Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of the rectum
- AJCC/UICC pathologic stages of cT3-4 or cN plus
- Male or female patients, 18 years of age or older
- Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- No prior chemotherapy, radiotherapy and immunotherapy
- Adequate major organ functions as following: Hematopoietic function: ANC (absolute neutrophil count)1,500/mm3, Platelet 100,000/mm3, and Hepatic function: serum bilirubin < 1.5 x ULN, AST/ALT levels < 2.5 x ULN, and Renal function: serum creatinine < 1.5 x ULN or Ccr 50 ml/min by Cockcroft formula
- Be willing and able to comply with the protocol for the duration of the study.
- Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
Exclusion Criteria:
- Any histologic feature other than adenocarcinoma or arisen from chronic inflammatory bowel disease
- Patients treated with previous surgery, chemotherapy and/or radiotherapy
- Uncontrolled or severe cardiovascular disease: New York Heart Association class III or IV heart disease, and Unstable angina or myocardial infarction within the past 6 months, and History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality.
- Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
- Other malignancy within the past 5 years except non-melanomatous skin cancer or carcinoma in situ of the cervix.
- Organ allografts requiring immunosuppressive therapy.
- Psychiatric disorder or uncontrolled seizure that would preclude compliance.
- Pregnant, nursing women or patients with reproductive potential without contraception.
- Patients receiving a concomitant treatment with drugs interacting with 5-FU or irinotecan such as flucytosine, phenytoin, or warfarin et al.
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Known hypersensitivity to any of the components of the study medications.
- Received any investigational drug or agent within 4 weeks before beginning treatment with study drug.
Sites / Locations
- Severance Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
5-FU with leucovorin
TS-1 with Irinotecan
Arm Description
Outcomes
Primary Outcome Measures
pathologic complete response rate
To evaluate pathologic complete response rate in patients with resectable rectal cancer teated with neoadjuvant chemoradiotherapy with 5-FU/leucovorin (FL) vs. TS-1/Irinotecan and surgery followed by fluoropyrimidine based adjuvant chemotherapy
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01269216
Brief Title
A Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer
Official Title
A Randomized Phase II Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, randomized phase II study. Patients will be randomly assigned to either FL or TS-1/irinotecan preoperative chemotherapy regimens by stratification. Patients in FL group will be treated with bolus injections of 5-FU 400 mg/m2/day and LV 20 mg/m2/day for 3 consecutive days every 4 weeks for 2 cycles, and patients in TS-1/irinotecan will be treated with irinotecan 40 mg/m2/day on days 1, 8, 15, 22, 29. TS-1 at a dose of 35mg/m2 was administered orally twice a day after a meal on the day of irradiation (Monday-Friday) concurrent with radiotherapy.
Detailed Description
This is an open-label, randomized phase II study. Patients will be randomly assigned to either FL or TS-1/irinotecan preoperative chemotherapy regimens by stratification. Patients in FL group will be treated with bolus injections of 5-FU 400 mg/m2/day and LV 20 mg/m2/day for 3 consecutive days every 4 weeks for 2 cycles, and patients in TS-1/irinotecan will be treated with irinotecan 40 mg/m2/day on days 1, 8, 15, 22, 29. TS-1 at a dose of 35mg/m2 was administered orally twice a day after a meal on the day of irradiation (Monday-Friday) concurrent with radiotherapy. Total 45-50.4 Gy radiations in 25-28 fractions to tumor and draining lymph nodes will be delivered concurrently. Curative surgery (especially total mesorectal excision will be considered as 1st choice of surgical procedure) will be performed for about 4-8 weeks after the completion of chemoradiotherapy. Postoperative chemotherapy regimen is 5-FU plus leucovorin.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5-FU with leucovorin
Arm Type
Active Comparator
Arm Title
TS-1 with Irinotecan
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
5-FU with leucovorin
Intervention Description
5FU 400mg/m2/day with Leucovorin 20mg/m2/day IV on day 1 and day29
Intervention Type
Drug
Intervention Name(s)
TS-1 with Irinotecan
Intervention Description
Irinotecan 40mg/m2/day IV on day 1,8,15,22 and 29 with TS-1 70mg/m2/day PO for 25 days
Primary Outcome Measure Information:
Title
pathologic complete response rate
Description
To evaluate pathologic complete response rate in patients with resectable rectal cancer teated with neoadjuvant chemoradiotherapy with 5-FU/leucovorin (FL) vs. TS-1/Irinotecan and surgery followed by fluoropyrimidine based adjuvant chemotherapy
Time Frame
every 4 weeks in FL group, every 2 weeks in TS-1/irinotecan group
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed adenocarcinoma of the rectum
AJCC/UICC pathologic stages of cT3-4 or cN plus
Male or female patients, 18 years of age or older
Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
No prior chemotherapy, radiotherapy and immunotherapy
Adequate major organ functions as following: Hematopoietic function: ANC (absolute neutrophil count)1,500/mm3, Platelet 100,000/mm3, and Hepatic function: serum bilirubin < 1.5 x ULN, AST/ALT levels < 2.5 x ULN, and Renal function: serum creatinine < 1.5 x ULN or Ccr 50 ml/min by Cockcroft formula
Be willing and able to comply with the protocol for the duration of the study.
Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
Exclusion Criteria:
Any histologic feature other than adenocarcinoma or arisen from chronic inflammatory bowel disease
Patients treated with previous surgery, chemotherapy and/or radiotherapy
Uncontrolled or severe cardiovascular disease: New York Heart Association class III or IV heart disease, and Unstable angina or myocardial infarction within the past 6 months, and History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality.
Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
Other malignancy within the past 5 years except non-melanomatous skin cancer or carcinoma in situ of the cervix.
Organ allografts requiring immunosuppressive therapy.
Psychiatric disorder or uncontrolled seizure that would preclude compliance.
Pregnant, nursing women or patients with reproductive potential without contraception.
Patients receiving a concomitant treatment with drugs interacting with 5-FU or irinotecan such as flucytosine, phenytoin, or warfarin et al.
Prior unanticipated severe reaction to fluoropyrimidine therapy, or known dihydropyrimidine dehydrogenase (DPD) deficiency.
Known hypersensitivity to any of the components of the study medications.
Received any investigational drug or agent within 4 weeks before beginning treatment with study drug.
Facility Information:
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
A Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer
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