Evaluation of Treatment Response With CHOI and RECIST Criteria and CT Texture Analysis in Patients With Metastatic Colorectal Cancer Treated With Regorafenib (TEXCAN)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
regorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring colorectal cancer, metastatic, regorafenib, CHOI criteria, RECIST criteria
Eligibility Criteria
Inclusion Criteria:
- Signed and dated informed consent.
- Patients with histologically proven metastatic colorectal cancer
- Patients previously treated with, or who are not considered candidates for available therapies, i.e., fluoropyrimidine-based chemotherapy, anti-VEGF therapy and anti-EGFR therapy (if patients were RAS wild-type).
- ECOG PS = 0 or 1
- Aged 18-years or older
- Life expectancy of at least 3 months
Adequate renal, bone marrow, liver and pancreatic functions:
- Estimated creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation
- Platelet count ≥ 100.000/mm3; hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1500/mm3. Transfusion to meet the inclusion criteria will not be allowed
- Total bilirubin ≤ 1.5 the upper limit of normal value (ULN); alanine aminotransferase (ALAT) and aspartame aminotransferase (ASAT) ≤ 3.0 x ULN (≤ 5.0 x ULN for patients with liver involvement of their cancer); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement of their cancer and/or have bone metastases)
- International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluation will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
- At least one target lesion on CT scan
- No contraindication to Iodine contrast media injection during CT.
- For women of childbearing potential, blood or urine pregnancy test performed a maximum of 7 days before start of study treatment and negative result documented before start of study treatment
- When applicable, i.e., women of childbearing potential having sexual activity, men having sexual activity, must agree to use an adequate contraception before entering the study, until at least 8 weeks after the last study drug administration
- Registration in a national health care system (CMU included).
Exclusion Criteria:
- 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 inclusion in the trial ; planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment
- Patients under judicial protection (curatorship, tutorship) and/or deprived of freedom
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication
- Pregnancy or breastfeeding
- Congestive heart failure ≥ New York Heart Association (NYHA) class 2
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
- Myocardial infarction less than 6 months before the start of study medication
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
- Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg despite optimal medical management)
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication
- Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2, NCI-CTCAE v 4.0 dyspnea)
- Ongoing infection >grade 2, NCI- CTCAE v 4.0
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])
- Known history of human immunodeficiency virus (HIV) infection
- Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy
- Patients with seizure disorder requiring medication
- History of organ allograft
- Patients with evidence or history of any bleeding diathesis, irrespective of severity
- Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 4.0 within 4 weeks prior to the start of study medication
- Non-healing wound, non-healing ulcer or non-healing bone fracture
- Dehydration grade ≥1, NCI-CTCAE v 4.0
- Known hypersensitivity to the study drug, study drug classes or excipient in the formulation
- Interstitial lung disease with ongoing signs or symptoms at the time of inclusion
- Persistent proteinuria >3.5 g/24 hour measured by urine protein-creatinine ratio from a random urine sample (≥ Grade 3, NCI-CTCAE v 4.0)
- Patients unable to swallow oral medication
- Any malabsorption condition
- Unresolved toxicity higher than Grade 1, NCI-CTCAE v 4.0, attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neuropathy
- Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks
- Treatment with any other investigational medicinal product within 28 days prior to study entry
- Chronic treatment potentially interacting with the study medication, i.e. strong CYP3A4 inducers/inhibitors, strong UGT1A9 inhibitors
Sites / Locations
- CHU Jean Minjoz
- Hôpitlal Henri Mondor
- Institut Hospitalier Franco-Britannique
- CHRU Claude Huriez
- ICM Val D'Aurelle
- Hôpital Pitié Salpêtrière
- Hôpital Saint Antoine
- Insitut Mutualiste Montouris
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Regorafenib
Arm Description
dose of regorafenib : 160mg once daily
Outcomes
Primary Outcome Measures
Tumor response rate at 2 months according Choi Criteria
Secondary Outcome Measures
Tumor response rate at 1 and 2 months according to RECIST1.1
Tumor response rate at 1 month according to Choi criteria
Best overall response rate (BOR) according to Choi criteria and to RECIST 1.1
Disease control rate (DCR)
Overall Survival (OS)
Progression free survival (PFS)
Specificity of Choi criteria at 1 month in identifying patients with long or short OS (using median OS as cut-off value).
Evaluation of tumor heterogeneity with TexRAD software
Threshold of the CTTA parameters (Skewness, Kurtosis, Entropy, Uniformity) provided by the TexRAD software at baseline and optimal variations of these parameters on the CT performed at one month (compared to baseline).
Serious adverse events( SAE) and adverse event (AE)
assessed by NCI-CTCAE4.0
Identify early prognostic biomarkers of regorafenib
Correlation between Baseline cell free DNA and survival outcomes (PFS and OS)
Full Information
NCT ID
NCT02699073
First Posted
February 23, 2016
Last Updated
February 26, 2019
Sponsor
GERCOR - Multidisciplinary Oncology Cooperative Group
1. Study Identification
Unique Protocol Identification Number
NCT02699073
Brief Title
Evaluation of Treatment Response With CHOI and RECIST Criteria and CT Texture Analysis in Patients With Metastatic Colorectal Cancer Treated With Regorafenib
Acronym
TEXCAN
Official Title
Evaluation of Treatment Response With CHOI and RECIST Criteria and CT Texture Analysis in Patients With Metastatic Colorectal Cancer Treated With Regorafenib. A GERCOR Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
July 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GERCOR - Multidisciplinary Oncology Cooperative Group
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate the performance of various tumor response criteria (Choi and RECIST1.1 criteria) in the assessment of regorafenib activity.
Moreover, an assessment of the tumor heterogeneity will be made using computed tomographic texture analysis (CTTA)
Detailed Description
This is a phase II study in patients with metastatic colorectal cancer treated by regorafenib.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
colorectal cancer, metastatic, regorafenib, CHOI criteria, RECIST criteria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regorafenib
Arm Type
Experimental
Arm Description
dose of regorafenib : 160mg once daily
Intervention Type
Drug
Intervention Name(s)
regorafenib
Intervention Description
160mg once daily during 3 weeks followed by 1 week off therapy.
Regorafenib will be taken until disease progression according to the CHOI and RECIST1.1 criteria, death or inacceptable toxicity.
Primary Outcome Measure Information:
Title
Tumor response rate at 2 months according Choi Criteria
Time Frame
2 months after the beginning of treatment
Secondary Outcome Measure Information:
Title
Tumor response rate at 1 and 2 months according to RECIST1.1
Time Frame
At 1 month and 2 months after the beginning of treatment
Title
Tumor response rate at 1 month according to Choi criteria
Time Frame
At 1 month after the beginning of treatment
Title
Best overall response rate (BOR) according to Choi criteria and to RECIST 1.1
Time Frame
BOR is the best response recorded from the strat of treatment until treatment failure up to 36 months
Title
Disease control rate (DCR)
Time Frame
DCR is the proportion of patient with tumor response (CR or RP) or tumor stabilization as best response from the inclusion until treatment failure, up to 36 months
Title
Overall Survival (OS)
Time Frame
Assessed from the date of study drug start to the date of patient death, due to any cause or to the last date the patient was known to be alive, up to 36 months
Title
Progression free survival (PFS)
Time Frame
PFS is the time from the date of study drug start to the date of progressive disease or death due to any cause, up to 36 months
Title
Specificity of Choi criteria at 1 month in identifying patients with long or short OS (using median OS as cut-off value).
Time Frame
At 1 month after inclusion
Title
Evaluation of tumor heterogeneity with TexRAD software
Description
Threshold of the CTTA parameters (Skewness, Kurtosis, Entropy, Uniformity) provided by the TexRAD software at baseline and optimal variations of these parameters on the CT performed at one month (compared to baseline).
Time Frame
At baseline and 1 month after inclusion
Title
Serious adverse events( SAE) and adverse event (AE)
Description
assessed by NCI-CTCAE4.0
Time Frame
Up to 36 months
Title
Identify early prognostic biomarkers of regorafenib
Time Frame
at baseline, Cycle 1 Day 15, cycle 2 Day 15 and end of treatment
Title
Correlation between Baseline cell free DNA and survival outcomes (PFS and OS)
Time Frame
at baseline, Cycle 1 Day 15, cycle 2 Day 15 and end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed and dated informed consent.
Patients with histologically proven metastatic colorectal cancer
Patients previously treated with, or who are not considered candidates for available therapies, i.e., fluoropyrimidine-based chemotherapy, anti-VEGF therapy and anti-EGFR therapy (if patients were RAS wild-type).
ECOG PS = 0 or 1
Aged 18-years or older
Life expectancy of at least 3 months
Adequate renal, bone marrow, liver and pancreatic functions:
Estimated creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation
Platelet count ≥ 100.000/mm3; hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1500/mm3. Transfusion to meet the inclusion criteria will not be allowed
Total bilirubin ≤ 1.5 the upper limit of normal value (ULN); alanine aminotransferase (ALAT) and aspartame aminotransferase (ASAT) ≤ 3.0 x ULN (≤ 5.0 x ULN for patients with liver involvement of their cancer); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement of their cancer and/or have bone metastases)
International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluation will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
At least one target lesion on CT scan
No contraindication to Iodine contrast media injection during CT.
For women of childbearing potential, blood or urine pregnancy test performed a maximum of 7 days before start of study treatment and negative result documented before start of study treatment
When applicable, i.e., women of childbearing potential having sexual activity, men having sexual activity, must agree to use an adequate contraception before entering the study, until at least 8 weeks after the last study drug administration
Registration in a national health care system (CMU included).
Exclusion Criteria:
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 inclusion in the trial ; planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment
Patients under judicial protection (curatorship, tutorship) and/or deprived of freedom
Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication
Pregnancy or breastfeeding
Congestive heart failure ≥ New York Heart Association (NYHA) class 2
Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
Myocardial infarction less than 6 months before the start of study medication
Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg despite optimal medical management)
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication
Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2, NCI-CTCAE v 4.0 dyspnea)
Ongoing infection >grade 2, NCI- CTCAE v 4.0
Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])
Known history of human immunodeficiency virus (HIV) infection
Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy
Patients with seizure disorder requiring medication
History of organ allograft
Patients with evidence or history of any bleeding diathesis, irrespective of severity
Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 4.0 within 4 weeks prior to the start of study medication
Non-healing wound, non-healing ulcer or non-healing bone fracture
Dehydration grade ≥1, NCI-CTCAE v 4.0
Known hypersensitivity to the study drug, study drug classes or excipient in the formulation
Interstitial lung disease with ongoing signs or symptoms at the time of inclusion
Persistent proteinuria >3.5 g/24 hour measured by urine protein-creatinine ratio from a random urine sample (≥ Grade 3, NCI-CTCAE v 4.0)
Patients unable to swallow oral medication
Any malabsorption condition
Unresolved toxicity higher than Grade 1, NCI-CTCAE v 4.0, attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neuropathy
Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks
Treatment with any other investigational medicinal product within 28 days prior to study entry
Chronic treatment potentially interacting with the study medication, i.e. strong CYP3A4 inducers/inhibitors, strong UGT1A9 inhibitors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry ANDRE, MD
Organizational Affiliation
Hôpital Saint Antoine
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Jean Minjoz
City
Besançon
Country
France
Facility Name
Hôpitlal Henri Mondor
City
Créteil
Country
France
Facility Name
Institut Hospitalier Franco-Britannique
City
Levallois Perret
Country
France
Facility Name
CHRU Claude Huriez
City
Lille
Country
France
Facility Name
ICM Val D'Aurelle
City
Montpellier
Country
France
Facility Name
Hôpital Pitié Salpêtrière
City
Paris
Country
France
Facility Name
Hôpital Saint Antoine
City
Paris
Country
France
Facility Name
Insitut Mutualiste Montouris
City
Paris
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35489233
Citation
Rousseau B, Boukerma AK, Henriques J, Cohen R, Lucidarme O, Borg C, Tournigand C, Kim S, Bachet JB, Mazard T, Louvet C, Chibaudel B, Vernerey D, Andre T, Hulin A. Impact of trough concentrations of regorafenib and its major metabolites M-2 and M-5 on overall survival of chemorefractory metastatic colorectal cancer patients: Results from a multicentre GERCOR TEXCAN phase II study. Eur J Cancer. 2022 Jun;168:99-107. doi: 10.1016/j.ejca.2022.03.009. Epub 2022 Apr 27.
Results Reference
derived
PubMed Identifier
31818317
Citation
Lucidarme O, Wagner M, Gillard P, Kim S, Bachet JB, Rousseau B, Mazard T, Louvet C, Chibaudel B, Cohen R, Garcia-Larnicol ML, Gobert A, Henriques J, Andre T. RECIST and CHOI criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with regorafenib, a prospective multicenter study. Cancer Imaging. 2019 Dec 9;19(1):85. doi: 10.1186/s40644-019-0271-z.
Results Reference
derived
Learn more about this trial
Evaluation of Treatment Response With CHOI and RECIST Criteria and CT Texture Analysis in Patients With Metastatic Colorectal Cancer Treated With Regorafenib
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