To estimate progression-free survival at one year in elderly patients with RAS/BRAF wild-type unresectable mCRC and good performance status treated with FOLFIRI + panitumumab as first-line therapy. The clinical hypothesis of this study is that the combination of panitumumab and FOLFIRI is a good treatment option in elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC. Another purpose of this clinical trial is to determine the RAS/BRAF mutation status in liquid biopsies at baseline and at the time of disease progression.
Phase II, multicentre, single-arm trial. Elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC will be evaluated before being included in this trial. Eligible patients will receive panitumumab plus FOLFIRI for disease control until disease progression, unacceptable toxicity, investigator decision or the patient's withdrawal of consent. Tumour response will be evaluated by investigators using RECIST criteria (Response Evaluation Criteria in Solid Tumours) version 1.1. Tumour response will be evaluated every 8 weeks until disease progression is documented. Disease response will be confirmed no less than 28 days after the criteria for response are first met. Radiographic progression of subjects with symptoms indicating disease progression will be evaluated at the time of symptom onset. Following disease progression, information will be collected on the subsequent lines of treatment chosen by the investigator and survival at follow-up visits held every 12 weeks (± 4 weeks) until completion of the trial (approximately 24 months after inclusion of the last patient in the trial). A blood sample will be taken at baseline and at the time of disease progression in order to determine the RAS/BRAF mutation status.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Panitumumab 6 mg/kg will be administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy
Irinotecan 150 mg/m2 will be administered as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle
Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1
5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
ICO L´Hospitalet de Llobregat - Hospital Durán i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Sant Joan Despí-Moises Broggi
Sant Joan Despí, Barcelona, Spain
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, Spain
Hospital Universitario Rey Juan Carlos
Móstoles, Madrid, Spain
Hospital Clínic
Barcelona, Spain
Hospital General Universitario de Elda
Elda, Spain
Hospital Universitario Arnau de Vilanova
Lleida, Spain
Hospital Universitario la Paz
Madrid, Spain
Hospital General Universitario Morales Meseguer
Murcia, Spain
Hospital Universitario Son Espases
Palma, Spain
...and 2 more locations
Progression-free survival at one year
Percentage of subjects still alive and progression free 12 months after inclusion in the study
Time frame: 12 months after inclusion
Progression-free survival (PFS)
Time (months) from inclusion in the trial until disease progression or death
Time frame: 42 months
Objective response rate
Proportion of patients with an objective response (complete or partial response) according to RECIST 1.1 criteria
Time frame: 42 months
Disease control rate
Proportion of patients with disease control (complete response, partial response or stable disease)
Time frame: 42 months
Duration of response
Time (months) from the first confirmation of objective response according to RECIST 1.1 criteria until disease progression or death
Time frame: 42 months
Time to response
Time (months) from inclusion in the trial until the date of the first confirmation of objective response according to RECIST 1.1 criteria
Time frame: 18 months
Overall survival (OS)
Time (months) from inclusion in the trial until death of the patient
Time frame: 42 months
Time to treatment failure
Time (months) from inclusion in the trial until progression, death or discontinuation due to toxicity
Time frame: 18 months
Proportion of patients with early tumour shrinkage (ETS)
Defined as tumour shrinkage ≥ 30% at the first tumour assessment based on RECIST 1.1 criteria
Time frame: 2 months
Depth of response (DpR)
Measured as the maximum reduction ratio (percentage) of the tumour compared with baseline measurement (sum of diameters of the lesions) at the different assessments based on RECIST 1.1 criteria
Time frame: 18 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence and severity of adverse events. AEs description according to the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time frame: 42 months
Combined analysis of prognostic factors in metastatic disease
To analyse the number of lesions in liver and lung disease (1-3 vs 4-9 or ≥10), and the size of the largest lesion (\<5 cm or ≥ 5 cm), in correlation with the analytical values, mainly LDH and AP values.
Time frame: 42 months
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