Panitumumab for Metastatic colorectal cancer (left-sided, RAS/BRAF wild-type)

Inclusion criteria

• {"criterion_text":"- Written informed consent to study procedures and to correlative studies"}
• {"criterion_text":"- Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory"}
• {"criterion_text":"- Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109 /L AND platelet count ≥ 100 x 109 /L AND hemoglobin ≥ 9 g/dL."}
• {"criterion_text":"- Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN"}
• {"criterion_text":"- Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula)"}
• {"criterion_text":"- Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range"}
• {"criterion_text":"- Histologically proven left sided mCRC"}
• {"criterion_text":"- RAS/BRAF wild-type and pMMR and/or MSS status assessed at local centers according to a validated method defined by EMA"}
• {"criterion_text":"- Disease judged unresectable by the local multidisciplinary team."}
• {"criterion_text":"- Patient candidate to receive Induction treatment with FOLFIRI plus panitumumab as per standard clinical practice"}
• {"criterion_text":"- No prior treatments (chemotherapy, radiation or surgery) for mCRC. Surgery for primary CRC tumor before starting treatment is allowed"}
• {"criterion_text":"- Either sex aged ≥ 18 years"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 at study entry"}
• {"criterion_text":"- Imaging-documented measurable disease, according to RECIST 1.1 criteria"}

Exclusion criteria

• {"criterion_text":"- Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer"}
• {"criterion_text":"- Participation in any interventional drug or medical device study within 30 days prior to treatment start"}
• {"criterion_text":"- Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment"}
• {"criterion_text":"- History of interstitial pneumonitis or pulmonary fibrosis"}
• {"criterion_text":"- History of corneal perforation or ulceration keratitis"}
• {"criterion_text":"- Prior chemotherapy or any other medical treatment for mCRC (previous adjuvant chemotherapy is allowed if terminated > 6 months previously)"}
• {"criterion_text":"- Major surgical intervention within 4 weeks prior to enrollment"}
• {"criterion_text":"- Pregnancy and breast-feeding"}
• {"criterion_text":"- Any brain metastases"}
• {"criterion_text":"- Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD) or known UGT1A1 homozygosity"}
• {"criterion_text":"- Required dose reduction of 5-fluorouracil in the past for toxicity"}
• {"criterion_text":"- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study"}
• {"criterion_text":"- History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form"}

Primary endpoints

• {"endpoint_text":"- Time to Treatment Failure (TTF) between the two arms: TTF is defined as the time from randomization to the objective disease progression by RECIST 1.1 criteria occurred during the treatment (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first, or a treatment delay > 28 days for toxicity","definition_or_measurement_approach":"Defined as time from randomization to objective disease progression by RECIST 1.1 during treatment (excluding progression during treatment-free intervals), or death from any cause, or treatment delay >28 days for toxicity."}

Secondary endpoints

• {"endpoint_text":"- Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1","definition_or_measurement_approach":"ORR assessed according to RECIST 1.1"}
• {"endpoint_text":"- Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response.","definition_or_measurement_approach":"Proportion of patients with complete response, partial response or stable disease as best response per RECIST."}
• {"endpoint_text":"- Depth of response (DpR) assessed as the percentage of tumor shrinkage observed at the lowest point (nadir) compared with baseline.","definition_or_measurement_approach":"Percentage tumor shrinkage at nadir compared with baseline."}
• {"endpoint_text":"- Progression-free survival (PFS) measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Time from randomization to first documented disease progression or death from any cause."}
• {"endpoint_text":"- Progression-free survival on treatment (PFSot) measured as the time from the date of randomization to the date of disease progression occurred during treatment or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Time from randomization to disease progression occurring during treatment or death from any cause."}
• {"endpoint_text":"- Overall survival (OS) calculated as the time from the date of randomization until the date of death from any cause.","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"- Safety evaluated as adverse events graded according NCI CTCAE v 5.0.","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v5.0"}
• {"endpoint_text":"- Tolerability evaluated as longitudinal toxicity over time and adverse event burden score.","definition_or_measurement_approach":"Longitudinal assessment of toxicity and AE burden scoring over time."}
• {"endpoint_text":"- Time toxicity measured as hospital-free days","definition_or_measurement_approach":"Measured as hospital-free days (time toxicity)."}
• {"endpoint_text":"- Quality of life (QoL) investigated through the EORTC QLQ-C30 and CR29 questionnaires-","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 and CR29 questionnaires."}
• {"endpoint_text":"- Patient Report Outcome (PRO)-CTCAE with items dedicated in particular to diarrhea and skin toxicity to evaluate the effect of the treatment on the health-related QoL","definition_or_measurement_approach":"Patient-reported outcomes via PRO-CTCAE focusing on diarrhea and skin toxicity."}
• {"endpoint_text":"- We will also explore the prognostic and predictive value of next generation sequencing (NGS), from blood samples (“liquid biopsy”) collected at baseline, at week 16 and thereafter every 8 weeks and serum metabolomic profiling in peripheral blood evaluated by NMR Spectrometer (600 MHz) concomitantly with tumor assessment, and at progression of disease. as well as the potential to monitor treatment activity of at baseline and during treatment.","definition_or_measurement_approach":"Exploratory biomarker analyses: NGS on blood samples (liquid biopsy) at baseline, week 16 and every 8 weeks, and serum metabolomic profiling by NMR at same timepoints and at progression."}

Italy

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

736

Number Of Participants

500

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy