Metastatic colorectal cancer in patients resectable or potentially resectable KRAS wild.
Conditions
Interventions
Trade Name: ERBITUX 5 mg/ml solución para perfusión
Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Other descriptive name: CE
Sponsors
ACROSS: Associació Catalana per a la Recerca Oncològica i les seves implicacions sanitàries i Socials
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Man or woman >= 18 years old 2.Able of understand, sign and date an informed consent form aproved by the ethics committee. 3.Metastasic colorectal cancer histologically confirmed by the investigator. 4.KRAS colorectal cancer (determined in primary tumor) with liver metastases limited to the liver, unresectable or potentially resectable, determined within the Multidisciplinary committee. 5.ECOG performance status (Eastern Cooperative Oncology Group)=1,5 x 109/L; platelets >= 100 x 109/L; hemoglobin >=9 g/dL. 7.Funtions hepatic, renal and metabolic, as follows: or adequate liver function: SAT (SGOT) and ALAT (SGPT) 2.5 x LSN (5 x LSN for liver metastases). Total bilirrubin = 50 mL/min.or Magnesium >= LIN, calcium >= LIN. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1.Presence of metastasic colorectal carcinoma with unresectable extrahepatic metastases. 2.Patients with a single resectable liver metastases. 3.Prior liver resection 4.Pre-existing clinically relevant (> grade 1) peripheral sensory neuropathy (e.g. paraesthesia, dysaesthesia). 5.The presence of active systemic infection at the time of inclusion in the study. 6.Patients who have had a myocardial infarction within the last twelve months before the start of the study or any other clinically rellevant cardiovascular disease. 7.Active inflammatory bowel disease or ileus 8.Any concurrent disease that may increase the rick of toxicity 9.Past or current history of neoplasm, except for curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years. 10.History of any disease that may increase the risks associated with study participation or may interfere with the interpretarion of study results. 11.Participation in a clinical trial administration of investigational drugs within 30 days prior to study entry. 12.Pregnant or breast-feeding, or planning to become pregnant within 6 months after the end of treatment. 13.Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, ie use 2 forms of birth control together, at least 1 of them barrier (eg., condom and control pills) or abstinence during the study and for 6 months after the last administration of study drug for womenn and 1 month for men. 14.The subject has a disorder of any kind that compromises their ability to provide written informed consent and / or comply with study procedures. 15.The subject is unwilling or unable to meet the requirements of the study. 16.The subject is not a candidate for surgery undergo liver metastases, according to the Committee's assessment Multidisciplinary
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To describe the histological response to Erbitux based chemotherapy in all excised liver metastases.;Secondary Objective: Kras status in excised liver metastases Histological responses in oxaliplatin and irinotecan groups Tumor thickness at interface tumor normal tissue in excised liver metastases Early radiological tumor shrinkage in liver metastases Early morphological response in liver metastases Whether there is a correlation between pathological response and metastasis Kras status, baseline metastasis size, radiological and morphological response in excised liver metastases If pathological and morphological responses correlate with disease free survival at 12 months Whether there is a correlation between early radiological tumor shrinkage and pathological responses of excised liver metastases Percentage severe perioperative AEs:anastomotic dehiscence,postoperative bile leakage,intrabdominal abscess,number of transfusions R0 rate,length of stay until hospital discharge,time from start chemotherapy to surgery,time from end chemotherapy to surgery in patients liver surgery;Primary end point(s): Pathological response will be assessed by pathologic evaluation of liver metastases, which will be performed centrally, and the degree of tumor regression. This evaluation will be performed according to Method Mandard in all the excised liver metastases, according to the following grades: 1.TRG1, absence of residual cancer and large amount of fibrosis 2.TRG2, rare residual cancer cells scattered throughout the fibrosis 3.TRG3, more residual tumor cells but fibrosis predominates; 4.TRG4, residual cancer cells predominate over fibrosis; and 5.TRG5, no signs of regression. Pathological response will be grouped as: 1.Major Histological Tumor Response (MjHR) including TRG1 and TRG2 2.Partial Histological Tumor Response (PHR) for TRG3 3.Non response (NHR) for TRG4 and TRG5 (3).;Timepoint(s) of evaluation of this end point: End of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.The percentage of Kras mutations determined with Therascreen in each of the liver metastases will be described. 2.Pathological responses will be described in the subgroups of patients receiving oxaliplatin and irinotecan based chemotherapies. 3.Tumor thickness and normal tissue interface in each tumor metastases excised. 4.At baseline and pre-surgery (at 8 weeks) radiological assessment with CT of the maximum diameter of each metastasis will be locally performed. 5.Morphological responses will be centrally assessed with the CT performed at 8 weeks. It will be locally performed 6.Disease Free Survival at 12 months. 7.Early tumor shrinkage. 8.R0 resection rate 9.Toxicity and adverse events at each visit 10. The hospital stay until discharge, the time from the start of chemotherapy to surgery, the time from the completion of chemotherapy to surgery in patients undergoing resection of liver metastases.;Timepoint(s) of evaluation of this end point: End of the study | — |
Countries
Spain
Contacts
Public ContactInmaculada Portal
ACROSS: Associació Catalana per a la Recerca Oncològica i les seves implicacions sanitàries i Socials
Outcome results
None listed