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A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab (DEEPER)

Primary Purpose

Colorectal Cancer

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
fluorouracil
Leucovorin
irinotecan
oxaliplatin
bevacizumab
cetuximab
Sponsored by
Japan Clinical Cancer Research Organization
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring FOLFOXIRI, Bmab, Cmab

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed colorectal cancer
  • RAS wild-type
  • Measurable lesion by RECIST (Ver.1.1)
  • No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS0.
  • Life expectancy of more than 6 months

  • Patients have enough organ function for study treatment within 14 days before enrollment;

    1. White blood cell (WBC)>=3,000/mm3, <12,000/mm3.
    2. Neu>=1,500/mm3.
    3. Platelet count (PLT) >=10.0x104/mm3.
    4. Hb>=9.0g/dL.
    5. Total Bilirubin<=1.5x Upper Limited Normal (ULN)
    6. aspartate aminotransferase (AST) <=2.5xULN.
    7. alanine aminotransferase (ALT) <=2.5xULN.
    8. Creatinine<=1.5xULN.
    9. Proteinuria<=1+.
    10. prothrombin time-international normalized ratio (PT-INR) <=1.5
  • Must be able to swallow tablets
  • Written informed consent

Exclusion Criteria:

  • Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
  • Lynch syndrome
  • Brain metastases
  • Infectious disease
  • Interstitial lung disease or pulmonary fibrosis
  • Comorbidity or history of serious heart failure
  • History of thromboembolic events
  • Cerebrovascular disease
  • History of hemoptysis/hematemesis
  • Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg)
  • Sensory alteration or paresthesia interfering with function
  • Large quantity of pleural, abdominal or cardiac effusion
  • Severe comorbidity (renal failure, liver failure, hypertension, etc)
  • Prior radiotherapy for primary and metastases leision
  • Men/women who are unwilling to avoid pregnancy
  • Women who are pregnant or breastfeeding
  • Women with a positive pregnancy test
  • History of severe allergy
  • HBsAg positive or active viral hepatitis
  • Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days
  • Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days
  • Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs)
  • Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy
  • History of gastrointestinal perforation within 1 year
  • Unhealed traumatic bone fracture
  • Uncontrolled diarrhea
  • History of organ recipient
  • Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded)
  • Administration of atazanavir sulfate
  • Jaundice
  • Ileus or bowel obstruction
  • Clinical diagnosis of Alzheimer's Disease
  • Insulin dependent diabetes
  • Thyroid disease
  • Any other cases who are regarded as inadequate for study enrollment by investigators

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    FOLFOXIRI+Bmab

    FOLFOXIRI+Cmab

    Arm Description

    Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.

    Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.

    Outcomes

    Primary Outcome Measures

    Best deepness of response
    The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments

    Secondary Outcome Measures

    Early tumor shrinkage
    The rates of tumor shrinkage by RECIST at 8 weeks
    Response rate
    Deepness of response
    The tumor shrinkage rates by RECIST at 4 months
    Overall survival
    Progression free survival
    Rate of curatively resected metastatic lesion
    Number of adverse events

    Full Information

    First Posted
    July 12, 2015
    Last Updated
    August 4, 2015
    Sponsor
    Japan Clinical Cancer Research Organization
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02515734
    Brief Title
    A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab
    Acronym
    DEEPER
    Official Title
    A Randomized Phase II Study to Investigate the Deepness of Response of FOLFOXIRI Plus Cetuximab (Erbitux) Versus FOLFOXIRI Plus Bevacizumab as the First-line Therapy in Metastatic Colorectal Cancer Patients With RAS Wild-type Tumors: DEEPER
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2015
    Overall Recruitment Status
    Unknown status
    Study Start Date
    August 2015 (undefined)
    Primary Completion Date
    December 2017 (Anticipated)
    Study Completion Date
    June 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Japan Clinical Cancer Research Organization

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.
    Detailed Description
    This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colorectal Cancer
    Keywords
    FOLFOXIRI, Bmab, Cmab

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    360 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    FOLFOXIRI+Bmab
    Arm Type
    Active Comparator
    Arm Description
    Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
    Arm Title
    FOLFOXIRI+Cmab
    Arm Type
    Experimental
    Arm Description
    Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
    Intervention Type
    Drug
    Intervention Name(s)
    fluorouracil
    Other Intervention Name(s)
    5-fluorouracil, 5-FU
    Intervention Type
    Drug
    Intervention Name(s)
    Leucovorin
    Other Intervention Name(s)
    Levofolinate
    Intervention Type
    Drug
    Intervention Name(s)
    irinotecan
    Other Intervention Name(s)
    CPT-11
    Intervention Type
    Drug
    Intervention Name(s)
    oxaliplatin
    Other Intervention Name(s)
    eloxatin
    Intervention Type
    Biological
    Intervention Name(s)
    bevacizumab
    Intervention Type
    Biological
    Intervention Name(s)
    cetuximab
    Primary Outcome Measure Information:
    Title
    Best deepness of response
    Description
    The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments
    Time Frame
    up to 2 years
    Secondary Outcome Measure Information:
    Title
    Early tumor shrinkage
    Description
    The rates of tumor shrinkage by RECIST at 8 weeks
    Time Frame
    at 8 weeks
    Title
    Response rate
    Time Frame
    up to 2 years
    Title
    Deepness of response
    Description
    The tumor shrinkage rates by RECIST at 4 months
    Time Frame
    at 4 months
    Title
    Overall survival
    Time Frame
    up to 2 years
    Title
    Progression free survival
    Time Frame
    up to 2 years
    Title
    Rate of curatively resected metastatic lesion
    Time Frame
    up to 2 years
    Title
    Number of adverse events
    Time Frame
    up to 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed colorectal cancer RAS wild-type Measurable lesion by RECIST (Ver.1.1) No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS0. Life expectancy of more than 6 months Patients have enough organ function for study treatment within 14 days before enrollment; White blood cell (WBC)>=3,000/mm3, <12,000/mm3. Neu>=1,500/mm3. Platelet count (PLT) >=10.0x104/mm3. Hb>=9.0g/dL. Total Bilirubin<=1.5x Upper Limited Normal (ULN) aspartate aminotransferase (AST) <=2.5xULN. alanine aminotransferase (ALT) <=2.5xULN. Creatinine<=1.5xULN. Proteinuria<=1+. prothrombin time-international normalized ratio (PT-INR) <=1.5 Must be able to swallow tablets Written informed consent Exclusion Criteria: Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval Lynch syndrome Brain metastases Infectious disease Interstitial lung disease or pulmonary fibrosis Comorbidity or history of serious heart failure History of thromboembolic events Cerebrovascular disease History of hemoptysis/hematemesis Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg) Sensory alteration or paresthesia interfering with function Large quantity of pleural, abdominal or cardiac effusion Severe comorbidity (renal failure, liver failure, hypertension, etc) Prior radiotherapy for primary and metastases leision Men/women who are unwilling to avoid pregnancy Women who are pregnant or breastfeeding Women with a positive pregnancy test History of severe allergy HBsAg positive or active viral hepatitis Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs) Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy History of gastrointestinal perforation within 1 year Unhealed traumatic bone fracture Uncontrolled diarrhea History of organ recipient Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded) Administration of atazanavir sulfate Jaundice Ileus or bowel obstruction Clinical diagnosis of Alzheimer's Disease Insulin dependent diabetes Thyroid disease Any other cases who are regarded as inadequate for study enrollment by investigators
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Masashi Fujii, MD
    Phone
    +81-3-5579-9882
    Email
    masashi.fujii@gioncology.jp
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sachika Koyama, Ms
    Phone
    +81-3-5579-9882
    Email
    cc13.dc@jaccro.or.jp
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Toshifusa Nakajima, MD
    Organizational Affiliation
    Japan Clinical Cancer Research Organization
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab

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