Unresectable stage III or stage IV cutaneous squamous cell carcinoma (cSCC) MedDRA version: 21.1 Level: PT Classification code 10041834 Term: Squamous cell carcinoma of skin System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: BAVENCIO
Product Name: Avelumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
CAS Number: 1537032-82-8
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Alcedis GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female subjects aged = 18 years on day of signing informed consent • Histologically proven cSCC in stage III, not amendable to surgery / curative radiation, or stage IV (according to the 8th AJCC edition; see chapter 18.6) • ECOG performance status of 0 or 1 • Measurable disease, i.e. at least one measurable lesion per RECIST, v1.1 • Required values for initial laboratory tests: o Absolute neutrophil count (ANC) = 1.5 × 10^9/L o Platelet count = 100 × 10^9/L o Hemoglobin = 9 g/dL (may have been transfused) o Total bilirubin level = 1.5 × the upper limit of normal (ULN) o ALT and AST = 2.5 × ULN (for subjects with documented metastatic disease to the liver: = 5 x ULN) o Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) • No active or chronic infection with HIV, Hepatitis B or C • Negative serum pregnancy test for women of childbearing potential • Highly effective contraception for both male and female patients throughout the study and for at least 30 days after last dose of study medication administration if the risk of conception exists. Highly effective contraception has to be in line with the definition of the CTFG (Clinical Trial Facilitation Group) recommendation (see 18.7) • Signed written informed consent and capacity of understanding the informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade = 3) • Patients with brain metastases • Current use of immunosuppressive medication, EXCEPT for the following: o Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) o Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent o Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. • Prior organ transplantation including allogeneic stem-cell transplantation • Active infection requiring systemic therapy • Known history of testing positive for HIV or known acquired immunodeficiency syndrome • Vaccination with any live vaccine (e.g. intranasal flu vaccine) within 4 weeks before the first dose of avelumab or planned vaccination with live vaccine during the trial • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable • Currently participating in or having participated in the treatment phase of a study of an investigational agent or using an investigational device within 4 weeks before registration and/or during study participation • Pregnancy or lactation period • Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent • Known alcohol or drug abuse • Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy in terms of objective response rate (ORR) after 3 months of combination therapy of avelumab and cetuximab according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);Secondary Objective: • To evaluate efficacy in terms of progression-free survival (PFS) of avelumab in combination with cetuximab • To evaluate efficacy in terms of duration of objective response (DOR) of avelumab in combination with cetuximab • To evaluate efficacy in terms of overall survival (OS) of of avelumab in combination with cetuximab • To evaluate the safety profile according to CTCAE, Version 5.0 criteria of avelumab in combination with cetuximab • To evaluate the Quality of Life (QoL) of cSCC patients treated with avelumab in combination with cetuximab by use of the QLQ-C30 questionnaire • To evaluate best objective response and PFS according to immune related response criteria (irRC) • To identify biomarkers including PD-L1, gene and protein expression, genetic alteration predictive to the combination treatment • To identify biomarkers in relation to disease responses to avelumab ;Primary end point(s): Objective response rate (ORR) after 3 months of cetuximab / avelumab combination therapy judged by investigator according to RECIST v1.1.;Timepoint(s) of evaluation of this end point: Clinical assessment of cutaneous tumor lesions, incl. photography and RECIST v1.1,will be determined at baseline, and every 6 weeks of therapy. Imaging procedures will be done at baseline, and every 12 weeks of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival - Duration of objective response - Overall survival - Safety Maximum CTAE grade per patient for AE, ADR, SAE and SADR - Quality of life Quality of life by use of the QLQ-C30 questionaire;Timepoint(s) of evaluation of this end point: - Overall response rate every 6 weeks as determined by RECIST 1.1 criteria - Overall survival: study enrolement until the day of progression/death - Safety: during the whole study - Quality of life: will be determined by use of the QLQ-C30 questionaire every 12 weeks | — |
Countries
Germany
Contacts
Public ContactUniversitätsklinik für Dermatologie
Johannes Wesling Klinikum Minden
Outcome results
None listed