Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 3816 for:    colon cancer AND Intestinal Neoplasms

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

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.
 
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

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.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Neoplasm Metastasis Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Biological: Bevacizumab Drug: CPT-11 (Irinotecan) Drug: 5-FU Bolus Drug: 5-FU Infusion Drug: l-LV (dl-LV) Biological: bevacizumab Drug: Capecitabine Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 650 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 2, 2013
Actual Primary Completion Date : November 20, 2017
Actual Study Completion Date : June 30, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
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
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

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
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT01996306


Locations
Layout table for location information
Japan
NPO Epidemiological and Clinical Research Information Network (ECRIN)
Kyoto, Japan, 606-8392
Sponsors and Collaborators
Epidemiological and Clinical Research Information Network
Investigators
Layout table for investigator information
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Epidemiological and Clinical Research Information Network
ClinicalTrials.gov Identifier: NCT01996306     History of Changes
Other Study ID Numbers: AXEPT
UMIN000012263 ( Other Identifier: UMIN )
First Posted: November 27, 2013    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019
Keywords provided by Epidemiological and Clinical Research Information Network:
AXEPT
Fluorouracil
CPT-11
XELIRI
Bevacizumab
FOLFIRI
Capecitabine
2nd-line metastatic colorectal cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Colorectal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Colonic Diseases
Intestinal Diseases
Neoplastic Processes
Pathologic Processes
Digestive System Diseases
Gastrointestinal Diseases
Rectal Diseases
Bevacizumab
Capecitabine
Irinotecan
Fluorouracil
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors