bevacizumab for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- 1.\tMale or female aged ≥18 years\n- 10.\tRAS/BRAF/EGFR/PIK3CAex20/ MAP2K1/MET WT and HER2 not amplified ctDNA at FoundationOne CDx test at baseline.\n- 11.\tLife expectancy of at least 3 months.\n- 12.\tAdequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).\n- 13.\tAdequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).\n- 14.\tAdequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).\n- 15.\tNo contraindication to the study drugs.\n- 16.\tNo prior treatment with trifluridine/tipiracil.\n- 17.\tWomen of childbearing potential* must have a negative blood pregnancy test at thescreening visit. Subjects and their partners must be willing to avoid pregnancy during the trial. *A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.\n- 18.\tWomen of childbearing potential, or male, must agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 6 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.\n- 19.\tWill and ability to comply with the protocol.\n- 2.\tEastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1\n- 20.\tSigned informed consent obtained before screening.\n- 3.\tDiagnosis of histologically or cytologically confirmed colorectal cancer.\n- 4.\tAt least one measurable lesion according to RECIST1.1\n- 5.\tKRAS/NRAS/BRAFV600E wt status of primary CRC or related metastasis (local laboratory assessment).\n- 6.\tProgression to previous first-line anti-EGFR-containing therapy producing at least a partial response ≥ 6 months.\n- 7.\tReceived and progressed to an anti-EGFR and irinotecan free second-line treatment.\n- 8.\tHave an anti-EGFR free interval of at least 4 months.\n- 9.\tRefractory to previous 5-fluorouracil/capecitabine, irinotecan, oxaliplatin, bevacizumab."}

Exclusion criteria

• {"criterion_text":"- ECOG PS ≥2\n- 10.\tDiagnosis of interstitial pneumonitis or pulmonary fibrosis.\n- 11.\tHistory of abdominal fistula, GI perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to the first study treatment.\n- 12.\tPregnant or lactating women.\n- 13.\tPsychiatric or addictive disorders would preclude study participation.\n- 14.\tActive uncontrolled infections or other clinically relevant concomitant illness contraindicating study treatments.\n- 15.\tWithdrawal of the consent to take part to the study.\n- 2.\tReceived more than 2 lines of treatment for metastatic disease.\n- 3.\tPrevious treatment with trifluridine/tipiracil\n- 4.\tRAS/BRAF/EGFR/PIK3CAex20/ MAP2K1/MET alterations and HER2 amplified tumors at liquid biopsy analysis during screening\n- 5.\tPrevious history of malignancy within the last 2 years will be excluded with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.\n- 6.\tEvidence of bleeding diathesis or coagulopathy.\n- 7.\tUncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.\n- 8.\tKnown severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).\n- 9.\tClinically significant cardiovascular disease, active inflammatory bowel disease, active autoimmune disease."}

Primary endpoints

• {"endpoint_text":"- ORR by RECIST 1.1 defined as the proportion of patients who have a partial or complete response to therapy. An external radiology department will receive the images of radiological re-evaluations from the participating sites. The imaging will be assessed by a blind operator","definition_or_measurement_approach":"ORR measured by RECIST 1.1 as the proportion of patients with partial or complete response; radiological re-evaluations images sent to an external radiology department and assessed by a blind operator."}

Secondary endpoints

• {"endpoint_text":"- 1.\tPFS defined as the time from random assignment in the clinical trial to disease progression or death from any cause.","definition_or_measurement_approach":"PFS measured as time from random assignment to disease progression or death from any cause."}
• {"endpoint_text":"- 2.\tOS defined as the interval from enrollment to death for every cause.","definition_or_measurement_approach":"OS measured as time from enrollment to death from any cause."}
• {"endpoint_text":"- 3.\tThe safety profile of the trial drugs as measured by the incidence of AEs evaluated using the NCI- CTCAE version 5.0 (CTCAE v 5.0), SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS","definition_or_measurement_approach":"Safety measured by incidence of AEs/SAEs per NCI CTCAE v5.0, laboratory assessments, vital signs, physical exams, ECG, and ECOG PS."}
• {"endpoint_text":"- 4.\tQuality of life (QoL) questionnaire (EORTC QLQ-C30)","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 questionnaire."}

Italy

Earliest CTIS Part Ii Submission Date

28-11-2025

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

52

Number Of Sites

26

Number Of Participants

150

Primary sponsor

Full Name

Gruppo Oncologico Dell'Italia Meridionale

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy