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
About this trial
This is an interventional basic science trial for Liver Metastases focused on measuring DWI-MRI, resectable liver metastases
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.
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
NCT ID
NCT02355353
First Posted
January 27, 2015
Last Updated
January 30, 2015
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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
Learn more about this trial
Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer
We'll reach out to this number within 24 hrs