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Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer

Primary Purpose

Liver Metastases, Colorectal Cancer

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Experimental: imaging arm
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Liver Metastases focused on measuring DWI-MRI, resectable liver metastases

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically proven CRC with metachronous or synchronous liver metastases considered to be completely upfront resectable.
  • Patients with at least one measurable liver lesion (> 2 cm), measured by contrast CT or MRI at baseline. At least one liver metastasis should be clearly identified and provide a high likelihood of successful resection in the later surgery.
  • Patients must be 18 years old or older.
  • A World Health Organization (WHO) performance status of 0 or 1.
  • Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 12 months before inclusion in this study.
  • All the following tests should be done within 6 weeks prior to registration:
  • Hematological status: neutrophils (ANC) ≥ 1.5x109/L; platelets ≥ 100x109/L; haemoglobin ≥ 9g/dL.
  • Serum creatinine ≤ 1.5 times the upper limit of normal (ULN).
  • No significant proteinuria (< 2+ proteinuria on urine dipstick or urine protein < 1g/24 hours urine collection).
  • Liver function: serum bilirubin ≤ 1.5 x ULN, alkaline phosphatase, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 5x ULN.
  • No hypercalcemia: ionized calcium ≤1.5 mmol/L.
  • Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable. This will not apply for Renal Function, including Creatinine.
  • Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 14 days before trial registration.
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • Before patient registration, written informed consent must be given according to International Conference on Harmonization of Good Clinical Practice (ICH/GCP), and national/local regulations.

Exclusion Criteria:

  • Evidence of extra-hepatic metastasis (of CRC).
  • Previous chemotherapy for metastatic disease or surgical treatment (e.g. surgical resection or radiofrequency ablation) for liver metastasis. Previous radiotherapy or embolization treatment on liver is not allowed.
  • Major surgical procedure, open biopsy, or significant traumatic injury in liver within 4 weeks prior to registration.
  • Other malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin.
  • Prior (less than 12 months prior to start treatment) or planned concurrent use of anti-angiogenic drugs such as bevacizumab in the back-bone chemotherapy
  • Prior (less than 12 months prior to start treatment) or planned concurrent use of anti-Epidermal Growth Factor Receptor (EGFR) monoclonal Antibody (mAb) such as panitumumab or cetuximab in the back-bone chemotherapy
  • Regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
  • Ongoing bleeding diathesis (e.g. hemoptysis of ≥ 1/2 teaspoon or 2.5 mL), coagulopathy, or need for administration of full-dose anti-coagulant(s).
  • Known history of myocardial infarction and/or stroke within 6 months prior to registration and /or New York Heart Association (NYHA) class III and IV congestive heart failure.
  • Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
  • History or evidence upon physical examination of Central Nervous System (CNS) metastasis.
  • Bowel obstruction.
  • Known allergy to any excipient of the standard chemotherapy agents
  • Known intolerance to atropine or loperamide.
  • Gilbert syndrome.
  • Treatment with Cytochrome P450 3A4 (CYP3A4) inducers, unless discontinued > 7 days prior to step 2 of registration.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Imaging arm

    Arm Description

    Outcomes

    Primary Outcome Measures

    Percentage of ADC changes
    Percentage of ADC changes at day 14 relative to baseline
    Tumor regression grade (TRG)
    Tumor regression grade (TRG) in the surgical resection specimen

    Secondary Outcome Measures

    Repeatability Coefficient
    Repeatability Coefficient from test-retest ADC measurements at baseline
    Pre-operative (post-treatment) ADC measurement
    Pre-operative (post-treatment) ADC measurement
    Lesion volume
    Lesion volume (baseline and, if applicable, after 3 cycles and after 6 cycles) using radiological assessment
    Histopathological measurements of tumor tissue cellularity /density, Necrosis, Proliferation (ki-67)
    Histopathological measurements on liver metastases Tumor tissue cellularity/density, Necrosis, Proliferation (ki-67)

    Full Information

    First Posted
    January 27, 2015
    Last Updated
    January 30, 2015
    Sponsor
    European Organisation for Research and Treatment of Cancer - EORTC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02355353
    Brief Title
    Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer
    Official Title
    Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer Treated With Fluoropyrimidine-based Chemotherapy as Preoperative Treatment
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2015
    Overall Recruitment Status
    Unknown status
    Study Start Date
    February 2015 (undefined)
    Primary Completion Date
    September 2016 (Anticipated)
    Study Completion Date
    February 2017 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    European Organisation for Research and Treatment of Cancer - EORTC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary objective of this study is to correlate the percentage change in apparent diffusion coefficient (ADC) between baseline and early therapy (at day 14) with tumor regression grade (TRG) measured in the surgical resection specimen.
    Detailed Description
    This is a prospective, multicenter, single-arm imaging trial. Patients with resectable liver metastases from colorectal cancer (CRC) will undergo Diffusion Weighted Imaging- Magnetic Resonance Imaging (DWI-MRI) scans at least at three separate occasions: at baseline, at 14 days (maximum +/- 1 days deviation is acceptable) after first administration of chemotherapy and finally after up to 6 cycles of chemotherapy (one week prior to surgery). All patients registered in the study may participate to the test-retest analysis. This analysis required a double baseline scans (called test-retest) to be done on two separate occasions, separated from each other by from one hour to one week but both before start of therapy. The repeated scan at baseline (retest) is optional as it will be used only for the test-retest repeatability analysis. Dedicated in-house developed software will be used to quantify ADC to assess tumor characteristics and response to therapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Liver Metastases, Colorectal Cancer
    Keywords
    DWI-MRI, resectable liver metastases

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    31 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Imaging arm
    Arm Type
    Experimental
    Intervention Type
    Other
    Intervention Name(s)
    Experimental: imaging arm
    Intervention Description
    DWI-MRI scans at baseline, at 14 days after first administration of chemotherapy and after up to 6 cycles of chemotherapy
    Primary Outcome Measure Information:
    Title
    Percentage of ADC changes
    Description
    Percentage of ADC changes at day 14 relative to baseline
    Time Frame
    at day 14 relative to baseline
    Title
    Tumor regression grade (TRG)
    Description
    Tumor regression grade (TRG) in the surgical resection specimen
    Time Frame
    After surgery, up to 22 weeks from baseline
    Secondary Outcome Measure Information:
    Title
    Repeatability Coefficient
    Description
    Repeatability Coefficient from test-retest ADC measurements at baseline
    Time Frame
    from test-retest ADC measurements at baseline
    Title
    Pre-operative (post-treatment) ADC measurement
    Description
    Pre-operative (post-treatment) ADC measurement
    Time Frame
    up to 21 weeks after baseline
    Title
    Lesion volume
    Description
    Lesion volume (baseline and, if applicable, after 3 cycles and after 6 cycles) using radiological assessment
    Time Frame
    AT baseline, after 9 weeks and after 18 weeks of chemotherapy
    Title
    Histopathological measurements of tumor tissue cellularity /density, Necrosis, Proliferation (ki-67)
    Description
    Histopathological measurements on liver metastases Tumor tissue cellularity/density, Necrosis, Proliferation (ki-67)
    Time Frame
    At baseline and up to 22 weeks after baseline

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically proven CRC with metachronous or synchronous liver metastases considered to be completely upfront resectable. Patients with at least one measurable liver lesion (> 2 cm), measured by contrast CT or MRI at baseline. At least one liver metastasis should be clearly identified and provide a high likelihood of successful resection in the later surgery. Patients must be 18 years old or older. A World Health Organization (WHO) performance status of 0 or 1. Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 12 months before inclusion in this study. All the following tests should be done within 6 weeks prior to registration: Hematological status: neutrophils (ANC) ≥ 1.5x109/L; platelets ≥ 100x109/L; haemoglobin ≥ 9g/dL. Serum creatinine ≤ 1.5 times the upper limit of normal (ULN). No significant proteinuria (< 2+ proteinuria on urine dipstick or urine protein < 1g/24 hours urine collection). Liver function: serum bilirubin ≤ 1.5 x ULN, alkaline phosphatase, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 5x ULN. No hypercalcemia: ionized calcium ≤1.5 mmol/L. Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable. This will not apply for Renal Function, including Creatinine. Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 14 days before trial registration. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Before patient registration, written informed consent must be given according to International Conference on Harmonization of Good Clinical Practice (ICH/GCP), and national/local regulations. Exclusion Criteria: Evidence of extra-hepatic metastasis (of CRC). Previous chemotherapy for metastatic disease or surgical treatment (e.g. surgical resection or radiofrequency ablation) for liver metastasis. Previous radiotherapy or embolization treatment on liver is not allowed. Major surgical procedure, open biopsy, or significant traumatic injury in liver within 4 weeks prior to registration. Other malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin. Prior (less than 12 months prior to start treatment) or planned concurrent use of anti-angiogenic drugs such as bevacizumab in the back-bone chemotherapy Prior (less than 12 months prior to start treatment) or planned concurrent use of anti-Epidermal Growth Factor Receptor (EGFR) monoclonal Antibody (mAb) such as panitumumab or cetuximab in the back-bone chemotherapy Regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Ongoing bleeding diathesis (e.g. hemoptysis of ≥ 1/2 teaspoon or 2.5 mL), coagulopathy, or need for administration of full-dose anti-coagulant(s). Known history of myocardial infarction and/or stroke within 6 months prior to registration and /or New York Heart Association (NYHA) class III and IV congestive heart failure. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy. History or evidence upon physical examination of Central Nervous System (CNS) metastasis. Bowel obstruction. Known allergy to any excipient of the standard chemotherapy agents Known intolerance to atropine or loperamide. Gilbert syndrome. Treatment with Cytochrome P450 3A4 (CYP3A4) inducers, unless discontinued > 7 days prior to step 2 of registration.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Oussama Karroum
    Phone
    003227741523
    Email
    oussama.karroum@eortc.be
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Sigrid Stroobants
    Organizational Affiliation
    Universitair Ziekenhuis Brussel
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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    Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer

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