Gemcitabine-UFTE Chemotherapy in Refractory Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01409005
Recruitment Status : Completed
First Posted : August 3, 2011
Last Update Posted : February 11, 2014
Seoul National University Hospital
SMG-SNU Boramae Medical Center
Yuhan Pharmaceutical Company
Jeil Pharmaceutical Company
Information provided by:
Seoul National University Bundang Hospital

Brief Summary:

Although there have been remarkable advances in the treatment of metastatic or recurrent colorectal cancer (MRCRC), long term survival cannot be expected in most patients with MRCRC because of inevitably developing resistance to chemotherapeutic drugs except some MRCRC patients who can undergo complete resection (metastasectomy). Until now, approved cytotoxic drugs for treatment of MCRC are only 3 categories (fluoropyrimidine, oxaliplatin and irinotecan). Recently, molecularly targeted drugs are approved for MRCRC patients, and bevacizumab and cetuximab (for K-ras wild type tumors) are available. When cytotoxic and targeted drugs are appropriately combined, about 24 months of overall survival (OS) can be expected in patients with MRCRC. However, when these drugs are all used or patients cannot afford to receive expensive targeted drugs because of economical problems, there is no option for chemotherapy and best supportive care is the only option, although some patients still have good performance status and medical conditions. Therefore, there are unmet needs for additional salvage chemotherapy regimens for patients with oxaliplatin, irinotecan and fluoropyrimidine-refractory MRCRC.

In some previous studies, gemcitabine-based chemotherapy showed some antitumor activities in MRCRC patients. Especially, when combined with fluoropyrimidine, gemcitabine has been shown to exert synergic effects on antitumor activities. On these backgrounds, this phase 2 clinical study was designed. In this study, efficacy and safety of gemcitabine plus UFTE chemotherapy will be evaluated in MRCRC patients.

Condition or disease Intervention/treatment Phase
Metastatic or Recurrent Colorectal Cancer Refractory to Fluoropyrimidine, Oxaliplatin and Irinotecan Salvage Chemotherapy Drug: Gemcitabine and UFTE chemotherapy Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Gemcitabine Plus UFTE Combination Chemotherapy as Salvage Treatment in Oxaliplatin, Irinotecan and Fluoropyrimidine-Refractory Metastatic Colorectal Cancer
Study Start Date : June 2011
Actual Primary Completion Date : February 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Gemcitabine plus UFTE
Gemcitabine plus UFTE chemotherapy (Single arm)
Drug: Gemcitabine and UFTE chemotherapy

Gemcitabine : 800 mg/m2 mix with 150mL of normal saline (i.v.) over 30 min on Days 1, 8 and 15

UFTE : 200mg/m2 PO q 8 hr, Days 1~21

Interval: every 4 weeks

Primary Outcome Measures :
  1. 8-weeks progression free survival rate (PFS rate) [ Time Frame: Response evaluation using computed tomography (CT) at 8 weeks after the initiation of chemotherapy ]
    % of patients without tumor prgression at 8 weeks after the initiation of chemotherapy

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: OS will be measured until death or study completion, with an expected average of 9 months ]
    OS will be measured until death of patients or study completion. Survival status will be followed up every 3 months if study treatment is completed.

  2. Response rate (RR) [ Time Frame: Response evaluation using CT will be performed every 8 weeks until tumor progression or death ]
    RECIST version 1.1 will be used for response evaluation

  3. Percentage of Patients with Adverse Events [ Time Frame: Overall safety will be monitored on every visit of patients during chemotherapy, with an expected average of 4 months ]
    Hematologic and non-hematologic toxicities will be evaluated.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: ≥ 18 years old
  • ECOG performance status: 0 to 2
  • Pathologically proven adenocarcinoma of colorectum
  • Patients who had received all cytotoxic drugs of 3 categories (fluoropyrimidine [5-FU, capecitabine or S-1 etc.], oxaliplatin and irinotecan).
  • Refractory MRCRC that progressed while receiving, or within 6 months after the discontinuation of all of fluoropyrimidine, oxaliplatin and irinotecan. When retry of fluoropyrimidine, oxaliplatin or irinotecan is not possible due to previous severe toxicities despite progression-free interval ≥ 6 months, patients can be enrolled into this study.
  • Patients who were previously treated with cetuximab or to whom cetuximab cannot be used (i.e. K-ras mutant or economical problems)
  • At least one measurable lesion should exist (RECIST version 1.1)

Exclusion Criteria:

  • Patients who had not previously received all of fluoropyrimidine, oxaliplatin and irinotecan will be excluded.
  • Patients who had received UFTE chemotherapy previously. However, if UFTE chemotherapy was used as adjuvant chemotherapy and the disease-free interval was greater than 6 months, the patient can be included into this study.
  • Patients receiving active or passive immunotherapy
  • Patients with complete bowel obstruction or progressive symptoms of partial bowel obstruction that interfere with adequate oral diet.
  • Patients with large amount of ascites requiring frequent therapeutic paracentesis (> once per week)
  • Pregnant or breast-feeding women (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study)
  • Women of child-bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period. Sexually active fertile men not using effective birth control during the study if their partners are women of child-bearing potential
  • Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy (i.e., uncontrolled infection, uncontrolled epilepsy, cerebrovascular accidents within the past 6 months, neurologic or psychological disease interfering with study treatment)
  • Inadequate cardiovascular function:

    • New York Heart Association class III or IV heart disease,
    • Unstable angina or myocardial infarction within the past 6 months,
    • Symptomatic coronary artery disease
    • History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality
  • Symptomatic severe interstitial lung disease or pulmonary fibrosis
  • Patients with impaired renal function: Creatinine clearance < 50mL/min (calculated by Cockcroft and Gault formula)
  • Patients with laboratory results as follows;

    • Number of absolute neutrophil counts (ANC) < 1.5 x 10^9/L
    • Number of thrombocytes < 100 x 10^9/L
    • Total bilirubin > 1.5 x upper limit of normal
    • ALAT, ASAT > 3 x upper limit of normal (in the cases with liver metastasis, > ALAT, ASAT > 5 x upper limit of normal)
    • Alkaline phosphatase > 3 x upper limit of normal (in the cases with liver or bone metastasis, > 5 x upper limit of normal)
  • Major surgery within 4 weeks of start of study treatment, without complete recovery
  • Patients who were included to other clinical trials within the past 4 weeks.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01409005

Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, Gyeonggi-do, Korea, Republic of, 463-707
Seoul National University Hospital
Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Seoul National University Bundang Hospital
Seoul National University Hospital
SMG-SNU Boramae Medical Center
Yuhan Pharmaceutical Company
Jeil Pharmaceutical Company
Principal Investigator: Jee Hyun Kim, M.D. & Ph.D. Professor, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine

Responsible Party: Jee Hyun Kim, Department of Internal Medicine, Seoul National University Bundang Hospital Identifier: NCT01409005     History of Changes
Other Study ID Numbers: CRC-SNU-2011-01
First Posted: August 3, 2011    Key Record Dates
Last Update Posted: February 11, 2014
Last Verified: January 2014

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs