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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02355353
• Other study ID #: EORTC-1423
• Status: Not yet recruiting
• Phase: N/A
• First received: January 27, 2015
• Last updated: January 30, 2015
• Start date: February 2015
• Est. completion date: February 2017

Study information

• Verified date: January 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: Oussama Karroum
• Phone: 003227741523
• Email: oussama.karroum[@]eortc.be
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 31
• Est. completion date: February 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis

Intervention

Other:
• Experimental: imaging arm
DWI-MRI scans at baseline, at 14 days after first administration of chemotherapy and after up to 6 cycles of chemotherapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of ADC changes	Percentage of ADC changes at day 14 relative to baseline	at day 14 relative to baseline	No
Primary	Tumor regression grade (TRG)	Tumor regression grade (TRG) in the surgical resection specimen	After surgery, up to 22 weeks from baseline	No
Secondary	Repeatability Coefficient	Repeatability Coefficient from test-retest ADC measurements at baseline	from test-retest ADC measurements at baseline	No
Secondary	Pre-operative (post-treatment) ADC measurement	Pre-operative (post-treatment) ADC measurement	up to 21 weeks after baseline	No
Secondary	Lesion volume	Lesion volume (baseline and, if applicable, after 3 cycles and after 6 cycles) using radiological assessment	AT baseline, after 9 weeks and after 18 weeks of chemotherapy	No
Secondary	Histopathological measurements of tumor tissue cellularity /density, Necrosis, Proliferation (ki-67)	Histopathological measurements on liver metastases Tumor tissue cellularity/density, Necrosis, Proliferation (ki-67)	At baseline and up to 22 weeks after baseline	No