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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by Yonsei University
Sponsor:
Information provided by (Responsible Party):
Yonsei University
ClinicalTrials.gov Identifier:
NCT01269216
First received: January 3, 2011
Last updated: March 20, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Drug: 5-FU with leucovorin
Drug: TS-1 with Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • pathologic complete response rate [ Time Frame: every 4 weeks in FL group, every 2 weeks in TS-1/irinotecan group ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 78
Study Start Date: October 2008
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01269216

Locations
Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Jae-Kyung Roh, MD, Ph.D    82-2-2228-8103    jkroh@yuhs.ac   
Sponsors and Collaborators
Yonsei University
  More Information

No publications provided

Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT01269216     History of Changes
Other Study ID Numbers: 4-2008-0361
Study First Received: January 3, 2011
Last Updated: March 20, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014