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Trial record 7 of 3787 for:    colon cancer AND Intestinal Neoplasms

A Phase III Study of 2nd-line XELIRI ± Bevacizumab vs. FOLFIRI ± Bevacizumab in mCRC (AXEPT)

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ClinicalTrials.gov Identifier: NCT01996306
Recruitment Status : Completed
First Posted : November 27, 2013
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Epidemiological and Clinical Research Information Network

Tracking Information
First Submitted Date  ICMJE November 22, 2013
First Posted Date  ICMJE November 27, 2013
Last Update Posted Date January 8, 2019
Actual Study Start Date  ICMJE December 2, 2013
Actual Primary Completion Date November 20, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2013)
Overall survival [ Time Frame: Assessed until 1.5 years after the last patient enrolment ]
Time from the date of enrollment to death from any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01996306 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2013)
  • Progression-free survival (PFS) [ Time Frame: Assessed until 1.5 years after the last patient enrolment ]
    Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
  • Time to treatment failure (TTF) [ Time Frame: Assessed until 1.5 years after the last patient enrolment ]
    Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment.
  • Overall Response Rate (ORR) [ Time Frame: Assessed at 6, 12 week and thereafter every 8 weeks ]
    Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician.
  • Disease Control Rate (DCR) [ Time Frame: Assessed at 6, 12 week and thereafter every 8 weeks ]
    Proportion of best overall response of CR, PR, or SD assessed by the attending physician.
  • Relative Dose Intensity [ Time Frame: Assessed until final dosing to the last patient ]
    will be calculated for each drug to evaluate treatment compliance in the all-treated population during the observation period.
  • Incidence of Adverse Events (Adverse Reactions) [ Time Frame: Adverse events occurring within 30 days after treatment discontinuation will be followed until recovery ]
    The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events.
  • Correlation between UGT1A1 genotype and safety [ Time Frame: Adverse events occurring within 30 days after treatment discontinuation will be followed until recovery ]
    The incidence of worst-grade adverse events on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm and UGT1A1 genotype in all treated patients with a known UGT1A1 genotype profile
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Study of 2nd-line XELIRI ± Bevacizumab vs. FOLFIRI ± Bevacizumab in mCRC
Official Title  ICMJE A Multinational, Randomized, Phase III Study of XELIRI With/Without Bevacizumab Versus FOLFIRI With/Without Bevacizumab As Second-line Therapy in Patients With Metastatic Colorectal Cancer
Brief Summary The primary purpose of this study is to determine the non-inferiority of overall survival XELIRI with or without Bevacizumab compared with FOLFIRI with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.
Detailed Description Primary endpoint: Overall survival (OS), Secondary endpoints: Progression-free survival (PFS), Time to treatment failure (TTF), Overall response rate (ORR),Disease Control Rate (DCR), Relative dose intensity, Safety, and Correlation between UGT1A1 genotype and Safety.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Intestinal Neoplasms
  • Gastrointestinal Neoplasms
  • Digestive System Neoplasms
Intervention  ICMJE
  • Biological: Bevacizumab
    5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.
    Other Name: Avastin
  • Drug: CPT-11 (Irinotecan)
    150-180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle.
    Other Name: Irinotecan
  • Drug: 5-FU Bolus
    400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.
    Other Name: fluorouracil
  • Drug: 5-FU Infusion
    2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.
    Other Name: fluorouracil
  • Drug: l-LV (dl-LV)
    200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.
    Other Name: Leucovorin
  • Biological: bevacizumab
    7.5mg/kg IV intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on Day 1 of a 3-week cycle.
    Other Name: Avastin
  • Drug: CPT-11 (Irinotecan)
    150-200 mg/m2 intravenously administered over 90 minutes on day 1 of a 3-week cycle.
    Other Name: Irinotecan
  • Drug: Capecitabine
    1600mg/m2/day oral on day 1 (evening) to day 15 (morning)of a 3-week cycle.
    Other Name: Xeloda
Study Arms  ICMJE
  • Active Comparator: FOLFIRI +/- Bevacizumab
    Bevacizumab 5 mg/kg IV 90-30 min Day 1 CPT-11 180 mg/m2 (150 mg/m2) IV 90 min Day 1 l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1 5-FU - bolus 400 mg/m2 IV bolus Day 1 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
    Interventions:
    • Biological: Bevacizumab
    • Drug: CPT-11 (Irinotecan)
    • Drug: 5-FU Bolus
    • Drug: 5-FU Infusion
    • Drug: l-LV (dl-LV)
  • Experimental: XELIRI +/- Bevacizumab
    Bevacizumab 7.5 mg/kg IV 90-30 min Day 1 CPT-11 200 mg/m2 (150 mg/m2) IV 90 min Day 1 Capecitabine 800 mg/m2 p.o. twice daily 14 Days consecutively
    Interventions:
    • Biological: bevacizumab
    • Drug: CPT-11 (Irinotecan)
    • Drug: Capecitabine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2016)
650
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2013)
600
Actual Study Completion Date  ICMJE June 30, 2018
Actual Primary Completion Date November 20, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
  2. Age ≥20 years at the time of informed consent
  3. ECOG performance status (PS) of 0-2
  4. Written informed consent prior to study-specific screening procedures
  5. Life expectancy of at least 90 days
  6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.
  7. Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL

Exclusion Criteria:

  1. History of other malignancy with a disease-free interval <5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
  2. With massive pleural effusion or ascites requiring intervention
  3. Radiological evidence of brain tumor or brain metastases
  4. Active infection including hepatitis
  5. Any of the following complication:

    i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)

  6. Any of the following medical history:

    Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency

  7. Previous treatment with irinotecan hydrochloride
  8. Current treatment with atazanavir sulfate
  9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
  10. Pregnant or lactating females, and males and females unwilling to use contraception
  11. Requires continuous treatment with systemic steroids
  12. Psychiatric disability that would preclude study compliance
  13. Otherwise determined by the investigator to be unsuitable for participation in the study
  14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
  15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
  16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
  17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
  18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease
  19. Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)
  20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
  21. Uncontrolled hypertension
  22. Urine dipstick for proteinuria >+2
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01996306
Other Study ID Numbers  ICMJE AXEPT
UMIN000012263 ( Other Identifier: UMIN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Epidemiological and Clinical Research Information Network
Study Sponsor  ICMJE Epidemiological and Clinical Research Information Network
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kei Muro, MD Aichi Cancer Center Hospital, Japan
Principal Investigator: Tae Won Kim, MD, PhD ASAN Medical center, South Korea
Principal Investigator: Young Suk Park, MD, PhD Samsung Medical Center, South Korea
Principal Investigator: Ruihua Xu, MD, PhD Sun Yat-Sen University Cancer Center, China
PRS Account Epidemiological and Clinical Research Information Network
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP