Pre-treated RAS/BRAF wild type metastatic colorectal cancer patients. MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Sponsors
GRUPPO ONCOLOGICO DELL'ITALIA MERIDIONALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management. 2. Male or female subjects aged = 18 years. 3. Histologically proven diagnosis of colorectal adenocarcinoma. 4. Diagnosis of metastatic disease. 5. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at initial diagnosis (according to NGS, Foundation/Roche). 6. Efficacy of a first line therapy containing cetuximab with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1). 7. Received a second line therapy. 8. More than 4 months since the last dose of cetuximab administered in first line treatment before randomization. 9. Measurable disease according to RECIST criteria v1.1. 10. ECOG PS of 0 to 1 at trial entry. 11. Estimated life expectancy of more than 12 weeks. 12. Adequate 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). 13. Adequate 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). 14. Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method). 15. Effective contraception for both male and female subjects throughout the study and for at least 2 months after last study treatment administration if the risk of conception exists. 16. No prior immunotherapy. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 73
Exclusion criteria
Exclusion criteria: 1. Any contraindication to cetuximab and/or avelumab. 2. Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix. 3. Pregnancy. 4. Breastfeeding. 5. Participation in a clinical study or experimental drug treatment within 30 days before enrollment. 6. Subjects receiving immunosuppressive agents (such as steroids) for any reason, should be tapered off these drugs before initiation of the trial treatment, 7. All subjects with brain metastases, except those meeting the following criteria: - Brain metastases have been treated locally - No ongoing neurological symptoms related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) 8. Prior organ transplantation, including allogeneic stem cell transplantation 9. Significant acute or chronic infections. 10. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent 11. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration ofsteroids will be completed in 14 days, or that the daily dose after 14 days will be = 10 mg per day of equivalent prednisone. 12. Known 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). 13. History of hypersensitivity to Polysorbate 80 that led to unacceptable toxicity requiring treatment cessation. 14. Persisting toxicity related to prior therapy of Grade > 1 NCI- CTCAE v 5.0. 15. Known alcohol or drug abuse. 16. Clinically significant (that is active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class = II), or serious uncontrolled cardiac arrhythmia requiring medication. 17. History of keratitis, ulcerative keratitis or severe dry eye. Since contact lent use is also a risk factor for keratitis and ulceration, it is not recommended. 18. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation ofstudy results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 19. Vaccination within 4 weeks of the first dose of avelumab and cetuximab and while on treatment is prohibited except for administration of inactivated vaccine (i.e. inactivated influenza vaccine) 20. Legal incapacity or limited legal capacity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of cetuximab plus avelumab (in terms of Overall Survival - OS) as rechallenge strategy in RAS/BRAF wild type metastatic (according to liquid biopsy at baseline) colorectal cancer patients as compared to cetuximab alone.;Secondary Objective: • To demonstrate superiority with regard to the Objective Response Rate (ORR) of avelumab and cetuximab combined in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients compared to cetuximab alone. • To demonstrate superiority with regard to Progression Free Survival (PFS) of avelumab and cetuximab combined in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients compared to cetuximab alone. • To determine the safety and tolerability of avelumab and cetuximab combined in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients as compared to cetuximab alone.;Primary end point(s): The primary endpoint for the trial is OS time, defined as the interval from enrollment to death for every cause.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 The Overall Response Rate (ORR) according to RECIST 1.1 defined as the proportion of patients who have a partial or complete response to therapy. 2 Progression Free Survival (PFS) according to RECIST 1.1 defined as the time from random assignment in the clinical trial to disease progression or death from any cause. 3 The safety profile of the trial drugs as measured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS;Timepoint(s) of evaluation of this end point: 1 12 and 24 months 2 12 and 24 months 3 Continuosly during the trial | — |
Countries
Italy
Contacts
Public ContactClinical Operations
Clinical Research Technology Srl
Outcome results
None listed