metastatic colorectal cancer MedDRA version: 20.0 Level: PT Classification code 10010035 Term: Colorectal cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colo
Conditions
Interventions
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: AVELUMAB
Current Sponsor code: MSB0010718C
Other descriptive name: Anti-PD-L1
Concentra
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with histologically confirmed, previously untreated RAS and BRAF wildtype, MSI or MSS metastastic colorectal cancer (primary tumor may be present) • Patients with at least one measurable lesion acc. to RECIST v1.1 • ECOG Performance status = 1 • Life expectancy > 3 months • Age = 18 years. • Haematologic function as follows: ANC = 1.5 x 10^9/L, platelets = 100 x10^9/L, hemoglobin = 9 g/dl or 5.59 mmol/l • Adequate liver function as measured by serum transaminases (AST & ALT) = 2.5 x ULN (in case of liver metastases =65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: • Malignancies other than disease under study within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent) • All subjects with known brain metastases, except those meeting the following criteria: o Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment o No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) o Subjects must be either off steroids or on a stable or decreasing dose of 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable. • All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma, colitis and pneumonitis), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment • Any psychiatric condition that would prohibit the understanding or rendering of informed consent • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines • Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 4 weeks prior to ini
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary clinical objective is to determine the efficacy of a standard 1st line regimen (FOLFOX and cetuximab) in patients with RAS/BRAF wildtype, MSI or MSS MCRC with avelumab in terms of progression free survival rate after 12 months (acc. to RECIST v1.1). ;Secondary Objective: The main secondary objective is to determine safety and tolerability, according to NCI CTC AE v4.03 and to the obtained data on vital signs, clinical parameters (oxygen saturation) and feasibility of the regimen. Further secondary objectives are to determine the efficacy of the experimental regimen in terms of objective response rate (acc. to RECIST v1.1 and irRECIST), and overall survival, to correlate clonal dynamics (RAS/EGFR subclones) with immune response signature to determine control of mutant subclones by the combination of anti-EGFR with anti-PD-L1and PD-L1 staining (and MSI status) with efficacy. ;Primary end point(s): The Progression Free Survival Rate at 12 months (primary endpoint) will be determined by the proportion of patients being alive without progressive disease 12 months after treatment start (according to RECIST v1.1). ;Timepoint(s) of evaluation of this end point: 12 months after treatment start | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • Safety and tolerability (acc. to NCI CTC AE v4.03 and to the obtained data on vital signs, clinical parameters (oxygen saturation) and feasibility of the regimen) • Response Rate (RR) according to RECIST v1.1 and modified RECIST (mRECIST) • Progression Free Survival (PFS) according to RECIST v1.1 and mRECIST • Overall survival (OS) • Translational research (correlation of clonal dynamics (RAS/EGFR subclones) with immune response signature to determine control of mutant subclones by the combination of anti-EGFR with anti-PD-L1, and PD-L1 (and MSI) status with efficacy ;Timepoint(s) of evaluation of this end point: - RR, PFS, OS: After LPLV | — |
Countries
Germany
Contacts
Public ContactDr. Aysun Karatas
AIO-Studien-gGmbH
Outcome results
None listed