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FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic 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.
 
ClinicalTrials.gov Identifier: NCT02128425
Recruitment Status : Unknown
Verified April 2014 by Yanhong Deng, Sun Yat-sen University.
Recruitment status was:  Recruiting
First Posted : May 1, 2014
Last Update Posted : May 7, 2014
Sponsor:
Information provided by (Responsible Party):
Yanhong Deng, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE April 15, 2014
First Posted Date  ICMJE May 1, 2014
Last Update Posted Date May 7, 2014
Study Start Date  ICMJE April 2014
Estimated Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2014)
Progression-free survival after induction and maintenance chemotherapy (PFS1) [ Time Frame: up to 18 months ]
Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months).
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2014)
Progression-free survival after re-introduction of chemotherapy (PFS2) [ Time Frame: up to 24 months ]
Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2014)
  • Progression-free survival after re-introduction of chemotherapy (PFS2) [ Time Frame: up to 24 months ]
  • Response rate during re-introduction of chemotherapy [ Time Frame: up to 12 months ]
    (CR + PR rate according to RECIST)
  • Early tumor shrinkage rate in 8 weeks after induction treatment [ Time Frame: 8 weeks ]
  • Overall survival [ Time Frame: up to 5 years ]
  • toxicity and safety [ Time Frame: up to 24 months ]
    Number of participants with adverse events as a measure of safety and tolerability according to NCI CTC 4.0
  • QLQ (QLQ C30) - scores according to EORTC QLQ-C30 scoring manual (Quality of life) [ Time Frame: up to 36 months ]
  • Translational research [ Time Frame: up to 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2014)
  • Progression-free survival between observation versus maintenance therapy (PFS1) [ Time Frame: up to 18 months ]
  • Response rate during re-introduction of chemotherapy [ Time Frame: up to 12 months ]
    (CR + PR rate according to RECIST)
  • Early tumor shrinkage rate in 8 weeks after induction treatment [ Time Frame: 8 weeks ]
  • Overall survival [ Time Frame: up to 5 years ]
  • toxicity and safety [ Time Frame: up to 24 months ]
    Number of participants with adverse events as a measure of safety and tolerability according to NCI CTC 4.0
  • QLQ (QLQ C30) - scores according to EORTC QLQ-C30 scoring manual (Quality of life) [ Time Frame: up to 36 months ]
  • Translational research [ Time Frame: up to 5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer
Official Title  ICMJE Phase II Randomized Controlled Trial of FOLFOXIRI Compared to FOLFOX in First Line Treatment of Chemo-naive Metastatic Colorectal Cancer
Brief Summary

The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of progression-free survival to conventional chemotherapy with the FOLFOX regimen as first-line treatment of chemo-naive metastatic colorectal cancer patients.

A second primary aim is to evaluate the response rate, safety and tolerability of the chemotherapy of FOLFOXIRI regimen in this patient population.

Patients will be randomized to two therapy groups:

Experimental arm A: Chemotherapy with FOLFOXIRI Standard arm B: Chemotherapy with FOLFOX

Detailed Description

Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs , but not with the proportion of patients who receive any second-line therapy. A superior efficacy in PFS,ORR and OS of FOLFOXIRI has been reported with acceptable toxicity. Moreover,evidence suggests that continuous dosing metronomic chemotherapy may be more efficacious than interval-chemotherapy.

Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a maintenance first-line regimen containing the three active agents.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: FOLFOXIRI

    irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 3200 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle

    *reduced in UGT1A1 7/7 patients

    Other Names:
    • Irinotecan
    • Oxaliplatin
    • Leucovorin
    • 5-Fluorouracil
  • Drug: FOLFOX
    oxaliplatin 85 mg/m² + leucovorin 400 mg/m² +5-FU 400mg/m² bolus iv.+ 5-FU 2400 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle
    Other Names:
    • Oxaliplatin
    • Leucovorin
    • 5-Fluorouracil
Study Arms  ICMJE
  • Experimental: FOLFOXIRI
    FOLFOXIRI
    Intervention: Drug: FOLFOXIRI
  • Active Comparator: FOLFOX
    FOLFOX
    Intervention: Drug: FOLFOX
Publications * Not Provided

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 6, 2014)
162
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2014)
164
Estimated Study Completion Date  ICMJE April 2018
Estimated Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent obtained before any study specific procedures. -Subjects must be able to understand and willing to sign a written informed consent.
  • Male or female subjects ≥ 18 years ≤ 75 years of age
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.(ECOG PS 0-2 for≥18 years ≤ 65 years of age ,ECOG PS 0-1 for >65 years of age)
  • Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
  • There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases (Histologic confirmation of metastasis is not required.).
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
  • No previous chemotherapy or target therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
  • In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
  • Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.
  • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
  • Alkaline phosphatase limit ≤ 5x ULN.
  • Amylase and lipase ≤ 1.5 x the ULN.
  • Serum creatinine ≤ 1.5 x the ULN.
  • Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.

Exclusion Criteria:

  • Previous palliative chemotherapy for metastatic disease,previous adjuvant chemotherapy including irinotecan or oxaliplatin within 6 months before random assignment.
  • Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
  • Life expectancy > 12 weeks;
  • Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.
  • Congestive heart failure ≤ New York Heart Association (NYHA) class 2.
  • Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.
  • Any evidence of active infection.
  • History of interstitial pneumonitis or pulmonary fibrosis
  • Pregnancy or lactation at the time of study entry.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study.
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea
  • Subjects with known allergy to the study drugs or to any of its excipients.
  • Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
  • Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (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 China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02128425
Other Study ID Numbers  ICMJE GIHSYSU06
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yanhong Deng, Sun Yat-sen University
Study Sponsor  ICMJE Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yanhong Deng, M.D. Sixth Affiliated Hospital, Sun Yat-sen University
PRS Account Sun Yat-sen University
Verification Date April 2014

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