Wild-type RAS metastatic colorectal cancer (mCRC) MedDRA version: 20.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: VECTIBIX 20mg/ml concentrado para solución para infusión
Product Name: PANITUMUMAB
Product Code: PANITUMUMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN:
Sponsors
ASOCIACION GITuD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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) 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 To estimate the overall response rate (ORR) To evaluate the disease control rate (DCR) To estimate the proportion of subjects with early tumour shrinkage (ETS) To evaluate the depth of response (DpR) To assess the duration of response (DoR) To assess the time to response (TTR) To estimate time to treatment failure (TTF) To estimate overall survival (OS) To assess the safety and tolerability 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Conversion rate of RAS status at disease progression (or end of second-line treatment for other reasons) from the status at second-line initiation. •Proportion of subjects with an objective response (complete or partial response) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria •Proportion of subjects with disease control (complete response, partial response or stable disease) •ETS with two cut-off set at 20% and 30% (RECIST 1.1) at the first tumour evaluation (week 8) •DpR measured as the maximum decrease in target measurement (RECIST1.1) all over the course of evaluation •DoR defined as time from first confirmed objective response to radiologic disease progression per RECIST 1.1 criteria or death. For participants who responded and have not progressed or died, duration of response will be censored at their last evaluable disease assessment date. •TTR defined as the time from second-line treatment initiation to the date of first confirmed objective response per RECIST 1.1 criteria. •TTF defined as the time from second-line treatment initiation until progression, death or discontinuation due to toxicity •OS defined as the time from the date of second-line treatment initiation to the date of death, with participants alive or lost to follow-up at the analysis data cut-off date censored at their last contact date •Safety assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03;Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Spain
Contacts
Public ContactClinical Operations
TRIAL FORM SUPPORT SL
Outcome results
None listed