A Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer

January 26, 2015 updated by: Yonsei University

A Randomized Phase II Study of Neoadjuvant Chemoradiotherapy With 5-FU/Leucovorin (FL) vs. TS-1/Irinotecan in Patients With Locally Advanced Rectal Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 5-FU with leucovorin
Drug: 5-FU with leucovorin
5FU 400mg/m2/day with Leucovorin 20mg/m2/day IV on day 1 and day29
Active Comparator: TS-1 with Irinotecan
Drug: TS-1 with Irinotecan
Irinotecan 40mg/m2/day IV on day 1,8,15,22 and 29 with TS-1 70mg/m2/day PO for 25 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pathologic complete response rate
Time Frame: every 4 weeks in FL group, every 2 weeks in TS-1/irinotecan group
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
every 4 weeks in FL group, every 2 weeks in TS-1/irinotecan group

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

January 3, 2011

First Submitted That Met QC Criteria

January 3, 2011

First Posted (Estimate)

January 4, 2011

Study Record Updates

Last Update Posted (Estimate)

January 28, 2015

Last Update Submitted That Met QC Criteria

January 26, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4-2008-0361

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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