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

Inclusion criteria

• {"criterion_text":"- 1. Written informed consent to study procedures and to correlative studies.\n- 2. Either sex aged ≥ 18.\n- 3. Histologically proven of colorectal adenocarcinoma\n- 4. Diagnosis of metastatic disease.\n- 5. RAS/BRAF wild-type status at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status.\n- 6. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at study entry (according to central testing).\n- 7. Efficacy of anti-EGFR drug in any line of treatment with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or stable disease ≥ 6 months.\n- 8. Received a subsequent line of therapy upon progression. Note. Patients must have received at least 2 lines of treatment. Previous treatment with regorafenib, trifluridine/tipiracile, fruquintinib is allowed. Previous rechallenge with anti-EGFR MoAb is NOT allowed. Adjuvant treatment will be considered as one line of therapy in case of progression within 6 months from the last dose of treatment.\n- 9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.\n- 10. Imaging-documented measurable disease, according to RECIST 1.1 criteria.\n- 11. Estimated life expectancy of more than 12 weeks.\n- 12. 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.\n- 13. 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.\n- 14. 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).\n- 15. Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range."}

Exclusion criteria

• {"criterion_text":"- 1. 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.\n- 2. Any contraindication to panitumumab or irinotecan.\n- 3. Not received immunotherapy if dMMR or MSI-H.\n- 4. Patients who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.\n- 5. Major surgical intervention within 4 weeks prior to enrollment.\n- 6. Pregnancy and breast-feeding.\n- 7. Any brain metastasis.\n- 8. Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc\n- 9. 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.\n- 10. 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.\n- 11. Participation in any interventional drug or medical device study within 30 days prior to treatment start.\n- 12. 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.\n- 13. History of interstitial pneumonitis or pulmonary fibrosis.\n- 14. History of corneal perforation or ulceration keratitis."}

Primary endpoints

• {"endpoint_text":"- Study Part 1_Progression-free survival (PFS) rate at 16 weeks: 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":"Measured as the time from randomization to first documented disease progression or death from any cause; PFS rate at 16 weeks."}
• {"endpoint_text":"- Study Part 2_PFS rate at 8 weeks: defined as the rate of assessable patients alive and not progressed after 8 weeks from initiation of VICTORIA - Study Part 2 (i.e End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1, for patients randomized to ARM A - standard treatment).","definition_or_measurement_approach":"Rate of assessable patients alive and without progression 8 weeks after initiation of Study Part 2 (as defined at End of Treatment Visit documenting progression to Study Part 1)."}

Secondary endpoints

• {"endpoint_text":"- Study Part 1: Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1.","definition_or_measurement_approach":"ORR per RECIST v1.1 (proportion achieving complete or partial response)."}
• {"endpoint_text":"- Study Part 1: 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 with CR/PR or stable disease as best response."}
• {"endpoint_text":"- Study Part 1: 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 progression or death."}
• {"endpoint_text":"- Study Part 1: 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":"- Study Part 1: Safety evaluated as adverse events graded according NCI CTCAE v. 5.0.","definition_or_measurement_approach":"AE reporting and grading per NCI CTCAE v5.0."}
• {"endpoint_text":"- Study Part 1: Quality of life (QoL) investigated through the EORTC QLQ-C30 and CR29 questionnaires.","definition_or_measurement_approach":"Patient-reported QoL using EORTC QLQ-C30 and CR29 instruments."}
• {"endpoint_text":"- Study Part 1: 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":"PRO-CTCAE items focused on diarrhea and skin toxicity."}
• {"endpoint_text":"- Study Part 2: Progression-free survival (PFS) measured as the time from the date from initiation of VICTORIA - Study Part 2 (i.e. at End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1) 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 initiation of Study Part 2 to progression or death."}
• {"endpoint_text":"- Study Part 2: Overall survival (OS) calculated as the time from the date from initiation of VICTORIA - Study Part 2 (i.e. at End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1) until the date of death from any cause.","definition_or_measurement_approach":"Time from initiation of Study Part 2 to death from any cause."}
• {"endpoint_text":"- Study Part 2: Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1.","definition_or_measurement_approach":"ORR per RECIST v1.1 in Study Part 2."}
• {"endpoint_text":"- Study Part 2: 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 with CR/PR or stable disease as best response in Study Part 2."}
• {"endpoint_text":"- Study Part 2: Safety evaluated as adverse events graded according NCI CTCAE v 5.0.","definition_or_measurement_approach":"AE reporting and grading per NCI CTCAE v5.0 in Study Part 2."}
• {"endpoint_text":"- Study Part 2: Quality of life (QoL) investigated through the EORTC QLQ-C30 and CR29 questionnaires.","definition_or_measurement_approach":"Patient-reported QoL using EORTC QLQ-C30 and CR29 in Study Part 2."}
• {"endpoint_text":"- Study Part 2: 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":"PRO-CTCAE items focused on diarrhea and skin toxicity in Study Part 2."}

Italy

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

658

Number Of Sites

10

Number Of Participants

130

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy