Multicenter prospective single-arm study investigating the efficacy and safety of second-line cetuximab plus chemotherapy treatment in initially RAS-mt mCRC patients who converted to RAS-wt at the time of first progressio
- Conditions
- patients with RAS-mt mCRC at diagnosis (based on tumor tissue) who convert to RAS-wt disease (based on ctDNA) at progression after first-line treatmentMedDRA version: 20.0Level: LLTClassification code 10079136Term: Adenocarcinoma of colon metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001328-36-IT
- Lead Sponsor
- MBERTO I - POLICLINICO DI ROMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 112
- Histologically proven diagnosis of colorectal adenocarcinoma;
- KRAS/NRAS-mt status of primary colorectal cancer and/or related metastasis; at the time of the initial diagnosis
- Radiological evidence of progression of disease (PD) after first-line therapy with chemotherapy plus bevacizumab;
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1);
- Male or female, aged > 18 years of age;
- ECOG Performance Status = 2;
- Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment;
Adequate bone marrow function (without hematopoietic growth factor or transfusion support within 14 days prior to study enrollment), including:
a. Absolute Neutrophil Count (ANC) ¿1,500/mm3 or ¿1.5 x 109/L.
b. Platelets ¿100,000/mm3 or ¿100 x 109/L.
c. Hemoglobin ¿9 g/dL (¿5.6 mmol/L).
Female patients of childbearing potential must have negative serum pregnancy or
urine pregnancy test at screening.
Adequate renal function defined by an estimated creatinine clearance ¿30 mL/min
according to the Cockcroft-Gault formula as:
•¿CLCR={[(140–age) × weight)]/(72 x SCR)} × 0.85 (if female), where CLCR
(creatinine clearance) is measured in mL/min, age is expressed in years, weight in
kilograms (kg), and SCR (serum creatinine) in mg/dL;
•¿Or as measured by 24h urine assessment.
Adequate liver function, including:
a. Total serum bilirubin ¿1.5 × the upper limit of normal range (ULN);
b. Aspartate and Alanine aminotransferase (AST and ALT) ¿2.5 x ULN.
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive;
- Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicidal or intrauterine device. This requirement begins 2 weeks before receiving the first trial treatment and ends 6 months after receiving the last treatment;
- Signed informed consent obtained before any study specific procedures.
- KRAS/NRAS-wt status, tested on ctDNA, at the time of progression after first line treatment
- Life expectancy of at least 3 months;
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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41
- 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;
- Women who are pregnant or are breastfeeding.
- Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration
- BRAF mutant tumors
- Known hypersensitivity to drugs used in this study or to any of the ingredients of these drugs
- eligeble potential patients must not be enrolled in clinicl trials which administered study drugs whithin 4 weeks prior to be enrolled in this trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Overall response rate (ORR) to cetuximab plus chemotherapy according to RECIST v1.1., that means the rate of patients with confirmed complete response (CR) or partial response (PR) as best response to treatment.;Secondary Objective: Progression free survival (PFS): measured as the time from the start of study treatment (second line therapy) until the first observation of disease progression or death due to any cause<br>Overall survival (OS): calculated as the time from the start of the study treatment (second line therapy) until death from any cause<br>Safety profile: adverse events graded according to NCI CTCAE v5.0;Primary end point(s): Overall response rate (ORR) to cetuximab plus chemotherapy according to RECIST v1.1., that means the rate of patients with confirmed complete response (CR) or partial response (PR) as best response to treatment.;Timepoint(s) of evaluation of this end point: 2 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -The duration of progression free survival (PFS)<br>-PFS: measured as the time from the start of study treatment (second line therapy) until the first observation of disease progression or death due to any cause; The duration of overall survival (OS)<br>OS: calculated as the time from the start of the study treatment (second line therapy) until death from any cause; The safety profile<br>Adverse events graded according to NCI CTCAE v5.0<br>Laboratory parameters;Timepoint(s) of evaluation of this end point: 2 months; from the start of the study treatment until the death; 2 months