metastatic colonrectal cancer KRAS, NRAS and BRAF wild type. MedDRA version: 17.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Irinotecan
Product Code: Irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IRINOTECAN
CAS Number: 97682-44-5
Concentration unit: g/ml gram(s)/mil
Sponsors
G.O.N.O. (Gruppo Oncologico Nord Ovest)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically proven diagnosis of colorectal adenocarcinoma; RAS and BRAF wild-type status of primary colorectal cancer and/or related metastasis; First-line irinotecan-based (FOLFIRI or FOLFOXIRI) cetuximab-containing therapy producing at least a partial response; First-line progression-free survival in response to cetuximab-containing therapy =6 months; Documentation of progression to first-line cetuximab within 4 weeks after last cetuximab administration; Time between the end of first-line therapy and the start of third-line treatment with cetuximab plus irinotecan =4 months; Second-line oxaliplatin-based (FOLFOXIRI, FOLFOX or XELOX) bevacizumab-containing therapy; Documentation of progression to second-line treatment; Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1); Have tumor tissue (of primary tumor and metastases or at least one of the two) available for biomarker analysis; Male or female, aged > 18 years of age; ECOG Performance Status = 2; Life expectancy of at least 3 months; Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment; Signed informed consent obtained before any study specific procedures. 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 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: Active uncontrolled infections or active disseminated intravascular coagulation; Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix; Fertile women (<12 months after last menstruation) and men of childbearing potential not willing to use effective means of contraception Woman who are pregnant or are breastfeeding Previous Grade 3/4 infusion related reaction to cetuximab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate, in terms of Overall Response Rate (ORR), the activity of cetuximab plus irinotecan as rechallenge third line treatment of RAS (K- and N-RAS, codons 12, 13, 59, 61, 117, 146) and BRAF (V600E) wild-type, irinotecan-resistant, mCRC patients progressing after an initial response to a first-line irinotecan- and cetuximab-containing therapy and a second-line with FOLFOXIRI/FOLFOX/XELOX plus bevacizumab.;Secondary Objective: the duration of progression-free survival (PFS); the duration of overall survival (OS); the safety profile; the evaluation of potential predictive and/or prognostic biomarkers ;Primary end point(s): The primary endpoint of this study is overall response rate (ORR) ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria. The determination of clinical response will be based on investigator-reported measurements. Responses will be evaluated with a chest and abdominal computed tomography (CT) scan every 8 weeks. Patients who do not have an on-study assessment will be included in the analysis as non-responders.;Timepoint(s) of evaluation of this end point: computed tomography (CT) scan every 8 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (PFS) is defined as the time from the start of therapy until the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on-study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression-free at the time of the analysis, or if lost to follow-up. Alive patients having no tumor assessments after baseline will have time to event endpoint censored on the date of treatment start . The determination of disease progression will be based on investigator-reported measurements. Disease status will be evaluated according to RECIST 1.1 criteria. Overall survival (OS) is defined as the time from the start of therapy until the date of death due to any cause. For patients still alive at the time of analysis, or if lost to follow up, the OS time will be censored on the last date the patients were known to be alive. Toxicity rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity V 4.03 ;Timepoint(s) of evaluation of this end point: For PFS from start treatment to disease progression or death due to any other causes. for OS from start treatment to death. | — |
Countries
Italy
Contacts
Public ContactU.O. Oncologia Medica Universit 2
Azienda Ospedaliero-Universitaria Pisana
Outcome results
None listed