This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVES: I. To evaluate whether treatment with avelumab plus cetuximab prolongs progression free survival (PFS) compared to avelumab alone. SECONDARY OBJECTIVES: I. To evaluate the confirmed objective response rate of each treatment arm. II. To evaluate the clinical benefit rate of each treatment arm. III. To evaluate the PFS of cetuximab plus avelumab in patients that have progressed on single agent avelumab. IV. To evaluate the overall survival (OS) for each treatment arm. V. To evaluate toxicity across treatment arms of avelumab plus cetuximab and avelumab alone. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to arm II. ARM II: Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months until disease progression, then every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Prolonging of progression free survival (PFS) on avelumab and cetuximab compared to avelumab alone
The study will be declared promising if, after the 37th PFS event, the hazard ratio is less than 0.758.
Time frame: Time between registration and evidence of disease progression or death, assessed up to 2 years post treatment
Confirmed objective response rate (RR)
A patient will be declared a success for RR if they achieve a partial response (PR) or better on two consecutive evaluations (at least 8 weeks apart). The number of successes will be divided by the number of evaluable patients to estimate the RR for each treatment arm and exact 95% confidence intervals will be calculated based on the properties of the binomial distribution.
Time frame: Up to 2 years post treatment
Clinical benefit rate (CBR)
The CBR is will be estimated as the number of successes divided by the total number of evaluable patients. An exact 95% confidence interval will be constructed around the CBR using the properties of the binomial distribution.
Time frame: Up to 2 years post treatment
PFS in patients who have progressed on avelumab alone
Will explore the PFS for those patients that crossover to combination therapy (avelumab + cetuximab) after progressing on avelumab alone (baseline time being the time of crossover). The Kaplan-Meier method will be used to calculate a median PFS as well as a 95% confidence interval.
Time frame: From time of enrollment to documented progression (or death), assessed up to 2 years
Overall Survival (OS)
The Kaplan-Meier method will be used to calculate a median OS as well as a 95% confidence interval.
Time frame: Time between enrollment and or death, assessed up to 2 years post treatment
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Incidence of adverse events
Will be described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Maximum grade adverse events will be summarized in a tabular setting by treatment arm.
Time frame: Up to 30 days post treatment