Analysis of 2nd line panitumumab + FOLFIRI efficacy in wild type RAS converted subjects from initially mutated RAS subjects with metastatic colorectal cancer treated in 1st line with standard FOLFOX + bevacizumab treatment.
- Conditions
- Wild-type RAS metastatic colorectal cancer (mCRC)MedDRA version: 20.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003242-25-ES
- Lead Sponsor
- ASOCIACION GITuD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1)Man or woman at least 18 years old
2)Capable of understand, sign and date an informed consent approved by an (Independent Ethics Committee) IEC
3)Histologically confirmed adenocarcinoma of the colon or rectum in subjects with unresectable metastatic (M1) disease
4)At least one unidimensionally measurable lesion of at least 10 mm per Response Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1)
5)Patients who received only one prior chemotherapy regimen for mCRC consisting of first-line FOLFOX+ bevacizumab
6)Radiographically confirmed disease progression after first-line FOLFOX + bevacizumab chemotherapy
7)Patients who had mutated RAS status confirmed as per standard of care according to international guidelines prior to first-line initiation
8)Patients candidate to second-line treatment and with wild-type RAS status in liquid biopsy confirmed prior to second-line initiation
9)Eastern Cooperative Oncology Group (ECOG) performance status 0-2
10)Adequate bone marrow function: neutrophils =1.5 x109/ L; platelets =100 x109/L; haemoglobin =9 g/dL
11)Hepatic, renal and metabolic function as follows:
- Total bilirubin count =1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 x ULN
- Renal function, calculated as creatinine clearance or 24-hour creatinine clearance = 50 mL/min
- Magnesium > lower limit of normal (LLN)
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1)History of prior or concurrent central nervous system (CNS) metastases
2)History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for = 5 years before the inclusion in the study
3)Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the subject unfit for inclusion
4)Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (eg, cetuximab) or prior irinotecan therapy
5)Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
6)History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerized tomography (CT)
7)Treatment for systemic infection within 14 days before the start of study treatment
8)Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade = 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03)
9)Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
10)History of Gilbert disease or known dihydropyrimidine deficiency syndrome
11)History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results.
12)Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
13)Any disorder that compromises the subject’s ability to provide written informed consent and/or comply with study procedures
14)Any investigational agent within 30 days prior to inclusion
15)Pregnant or breastfeeding woman
16)Major surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
17)Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men
18)The subject is unwilling or unable to meet the requirements of the study
19)Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule. These conditions should be discussed with the subject before inclusion in the trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To estimate progression-free survival (PFS) in second- line treatment with panitumumab + FOLFIRI in wild type RAS mCRC patients who had mutant RAS at initiation of the first-line (standard FOLFOX + bevacizumab treatment);Secondary Objective: To estimate the conversion rate from wild tpe to mutant RAS status at disease progression after second-line treatment<br>To estimate the overall response rate (ORR)<br>To evaluate the disease control rate (DCR)<br>To estimate the proportion of subjects with early tumour shrinkage (ETS)<br>To evaluate the depth of response (DpR)<br>To assess the duration of response (DoR)<br>To assess the time to response (TTR)<br>To estimate time to treatment failure (TTF)<br>To estimate overall survival (OS)<br>To assess the safety and tolerability <br>Biomarkers analysis by liquid bipsies;Primary end point(s): PFS defined as the time from second-line initiation to progression or death.;Timepoint(s) of evaluation of this end point: End of Study
- Secondary Outcome Measures
Name Time Method