METASTATIC COLORECTAL CANCER MedDRA version: 21.0 Level: LLT Classification code 10001172 Term: Adenocarcinoma of colon stage IV System Organ Class: 100000004864
Conditions
Interventions
Trade Name: VECTIBIX - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO 1 FLACONCINO (VETRO) 20 ML
Product Name: PANITUMUMAB
Product Code: [ABX-EGF]
Pharmaceutical Form: Solution for
Sponsors
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCCS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of metastatic colorectal cancer; 2. Age = 18 years; 3. Written informed consent; 4. Documented WT RAS exons 2, 3 and 4 (KRas and NRas) and WT BRAF V600E for anti-EGFR treatment. 5. Complete or partial response to anti EGFR antibodies in any line either received as monotherapy or in combination with chemotherapy; 6. Imaging documented progression while on therapy with a therapeutic regimen including anti-EGFR mAb; 7. Imaging documented progression at the last treatment regimen that must be anti-EGFR free; 8. Patient must be RAS and EGFR ectodomain wild type in a liquid biopsy performed no longer that 4 weeks after progression to the last anti-EGFR free treatment 9. FFPE sample used for eligibility to anti-EGFR prescription (see criteria 4) must be available for custom gene panel profiling (as described in appendix B). Otherwise if sample is not available, center must have already perfomed a genotyping on this tissue sample according to appendix B. 10. ECOG performance status = 2; 11. At least one measurable tumor lesion as per RECIST v1.1. Lesions in previously irradiated areas or those that have received other loco-regional therapies (i.e. percutaneous ablation) should not be considered measurable unless there is clear documented evidence of progression of the lesion since therapy. Imaging must be performed maximum within 28 days prior to registration; 12. Normal organ functions; 13. Negative serum pregnancy test within 1 week prior to the first study dose in all women of childbearing potential; 14. Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception; 15. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. 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 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1. History of severe infusion reactions to monoclonal antibodies cetuximab or panitumumab; 2. Symptomatic or untreated leptomeningeal disease and symptomatic brain metastasis; 3. Clinically significant cardiac disease including: a. congestive heart failure requiring treatment (NYHA grade = 2), Left ventricular ejection fraction (LVEF) 480 msec; 4. History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism; 5. Patients with interstitial pneumonitis or pulmonary fibrosis; 6. Abnormal organ or bone marrow functions defined as: a. Absolute neutrophil count 2.5 x upper normal limit (ULN), if liver metastases > 5 x ULN; d. aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2.5 x ULN, if liver metastases > 5 x ULN; e. bilirubin > 1.5 x ULN, if liver metastases > 2 x ULN; f. serum creatinine > 1.5 x ULN and/or creatinine clearance = 50 mL/min calculated according to Cockroft-Gault; g. Patients with platelet count <100 x 10^9/L 7. Previous or concurrent second malignancy. Exceptions: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively and without evidence of recurrence for at least 3 years prior to study entry. 8.Patients with positive serology for HIV, HBV, HCV. 9. Patients with a history of severe or life threatening hypersensitivity to the active substance or to any of the excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of a third-line Panitumumab re-challenge in patients with metastatic colorectal cancer (mCRC), originally responsive to anti EGFR therapy, selected on the basis of RAS extended clonal evolution in plasma.;Secondary Objective: •To assess Progression Free Survival (PFS) and Overall Survival (OS) after panitumumab re-challenge. •To determine the safety and tolerability of panitumumab re-challenge. • Translational Objectives: 1) To correlate the decay kinetics of RAS-extended clone(s) during anti-EGFR treatment holiday with response to panitumumab rechallenge. 2) To link the blood-presence of RAS-extended clone(s) (if any) during panitumumab treatment with response and response duration. 3) To describe by NGS the tumor ctDNA plasma landscape before and after panitumumab re-challenge. 4) To determine potential associations, if existing, between different mutated ctDNA clones (RAS or others) and response to panitumumab re-challenge. ;Primary end point(s): Overall response rate (ORR) to panitumumab according to RECIST v1.1.;Timepoint(s) of evaluation of this end point: Q8 WEEKS (+/- 3 DAYS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PROGRESSION FREE SURVIVAL (PFS); OVERALL SURVIVAL (OS); INTENSITY AND FREQUENCY OF THE ADVERSE EVENTS ACCORDING TO CTCAE V. 4.03.; Longitudinal extended RASmut ctDNA levels in plasma by ddPCR (end point related to translational objectives 1 and 2). ; Plasma ctDNA landscapes by NGS Candiolo Panel at panitumumab baseline and progression (end point related to translational objectives 3 and 4). ;Timepoint(s) of evaluation of this end point: Q8 WEEKS (+/- 3 DAYS); THROUGHOUT THE STUDY; THROUGHOUT THE STUDY.; Q2 weeks; At baseline and at disease progression. | — |
Countries
Italy
Contacts
Public ContactCLINICAL RESEARCH OFFICE
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA
Outcome results
None listed