Metastatic Colorectal Cancer, RAS Wild Type
Conditions
Brief summary
This is a non-profit phase II, open-label, single-arm study of cetuximab plus avelumab in patients with RAS WT mCRC treated in first line with chemotherapy in combination with an anti- EGFR drug that have had a clinical benefit (complete or partial response) from treatment.
Detailed description
The primary objective of the study is to evaluate the efficacy (OS) of avelumab and cetuximab combined in pre-treated RAS wild type metastatic colorectal cancer patients. Tumor measurements by computed tomography (CT) scan or magnetic resonance imaging (MRI) will be performed every 8 weeks from the beginning of treatment to determine response to treatment. Response will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Treatment will continue until disease progression, significant clinical deterioration, unacceptable toxicity, any criterion for withdrawal from the trial or trial drug is fulfilled. Treatment may continue past the initial determination of disease progression per RECIST 1.1 if the subject's performance status has remained stable, and if in the opinion of the Investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol.
Interventions
DRUGAvelumab
avelumab in combination with cetuximab
DRUGCetuximab
avelumab in combination with cetuximab
Sponsors
University of Campania Luigi Vanvitelli
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
combination treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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) wild-type in tissue at initial diagnosis. 6. Efficacy of a first line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with a major response achieved (complete or partial response). 7\. A second line therapy. 8. More than 4 months from last dose of anti-EGFR agent 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 if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.) Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists. 16\. No prior immunotherapy
Exclusion criteria
Subjects are not eligible for this trial if they fulfill any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall survival | 24 months |
Countries
Italy
Outcome results
None listed