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Phase 1
Conditions
Patients with liver-only non resectable colorectal metastases.
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2016-001493-15-FR
Lead Sponsor
ICANCER
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Not specified
Target Recruitment
140
Inclusion Criteria

1.Histologically confirmed colorectal cancer (CRC), and radiologic or histologic proof of CRLM
not amenable to a curative intent-treatment after two months to 6 months of first-line induction CT
2.First-line CT with oxaliplatin and/or irinotecan combined with a fluoropyrimidine and a targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) for metastatic disease (patients ending their adjuvant chemotherapy after primary tumor resection since less than 6 months should also have received first-line chemotherapy for metastatic disease)
3.Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria):
-Upfront R0/R1 resection of all CRLM (that leaves at least two adequately perfused and drained segments) is not possible
-and/or metastases in contact with major vessels of the remnant liver which would require resection of the vessel for an R0 resection (i.e., tumor involvement of main portal right and left portal veins, of the three main hepatic veins, or of the retrohepatic vena cava)
-and/or documented progressive disease on imaging (according to the RECIST v1.1 criteria) or doubling of serum levels of carcinoembryonic antigen (CEA) or CA 19.9 following = 2 months of induction CT
4.At least one measurable liver metastasis according to the RECIST v1.1
5.Age = 18 years
6.ECOG performance status 0-1
7.Normal liver function, i.e. bilirubin < 1.5 times the upper limit of normal values (ULN), aminotransferases < 5 ULN, alkaline phosphatase < 5 ULN
8.International normalized ratio (INR) < 1.5 ULN
9.Neutrophils > 1500/mm3, platelets > 100 000/mm3, hemoglobin > 9 g/dL (transfusion allowed)
10.Calculated creatinine clearance > 50 mL/min (Cockcroft and Gault formula)
11.Informed consent signed by the patient or his/her legal representative
12.Patient affiliated to a social security regimen
13.Adequate contraception if applicable

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

NON-INCLUSION CRITERIA:
1. Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review.
2. Extrahepatic tumor disease (except = 3 lung nodules < 10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms)
3. Patient with contraindication for trial drugs (investigators have to refer to drugs SmPC, see appendix 1); contraindication limited to targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) is not an exclusion criteria
4. Sensory neuropathy = grade 2 (NCI-CTAE v.4.0)
5. Significant chronic liver disease (resulting in portal hypertension and/or liver insufficiency)
6. Allergy to contrast media that cannot be managed with standard care
7. Previous organ transplantation, HIV or other immunodeficiency syndromes
8. Concomitant or past history of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix
9. Concomitant medications/comorbidities that may prevent the patient from receiving study treatments as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension…)
10. Ionic disorders as:
• Kalemia = 1 x ULN
• Magnesemia < 0.5 mmol/L
• Calcemia < 2 mmol/L
11. Patient with known dihydropyrimidine dehydrogenase deficiency
12. QT/QTc > 450 msec for men and > 470 msec for women
13. Concomitant intake of St. John's wort
14. Patient already included in another clinical trial with an experimental treatment
15. Pregnancy or lactation
16. Patients deprived of liberty or under guardianship
17. Patients unable to undergo medical monitoring test for geographical, social or psychological reasons

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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