A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer

Study Overview
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Brief Summary
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The purpose of the study is to see if the combination of radiation therapy and cemiplimab immunotherapy is an effective treatment for people with locally advanced, unresectable CSCC.

Official Title
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A Phase II, Multicenter, Single-Arm Clinical Trial of Radiotherapy and CeMiPlimAb: Rwlc ImmunoTherapy for Locally Advanced, Unresectable Cutaneous Squamous Cell Carcinoma: RAMPART

Conditions
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Locally Advanced Skin Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Skin Cancer, Squamous Cell Carcinoma, Locally Advanced Squamous Cell Carcinoma, Locally Advanced Squamous Cell Carcinoma of the Skin, Locally Advanced Cutaneous Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cemiplimab
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven cutaneous squamous cell carcinoma which is locally advanced Mixed histology tumors that are predominantly squamous cell carcinoma are eligible Locally advanced primary tumor is T3-T4 and/or N+ by AJCC and/or UICC 8th edition clinical criteria T3-T4 primary tumor characteristics noted below: Non-eyelid tumor >4 cm in maximum dimension or with bone erosion or invasion, perineural invasion of nerve 0.1 mm or larger, or invasion beyond subcutaneous fat or >6 mm from granular layer of adjacent normal epidermis Eyelid tumor >2 cm or invading adjacent ocular, orbital or facial structures ≥18 years old Unresectable or medically inoperable according to local multidisciplinary consensus for reasons such as: Tumor or regional lymph node metastases that has recurred despite ≥2 prior surgical procedures, with another curative resection unlikely Tumor or nodal disease with significant local invasion that precludes complete resection Tumor or nodal disease in anatomically challenging area where surgery may result in significant disfigurement or dysfunction (amputation of nose, ear, eye, digit, limb, etc) Medical contraindication to surgery Patient refusal of surgery due to anticipate morbidity ECOG ≤2 Adequate bone marrow and metabolic function (by blood tests) Total bilirubin ≤1.5 x upper limit of normal Aspirate aminotransferase (AST) ≤3 x upper limit of normal Alanine aminotransferase (ALT) ≤3 x upper limit of normal Alkaline phosphatase ≤2.5 x upper limit of normal Serum creatinine ≤1.5 x upper limit of normal or estimated creatinine clearance >30 mL/min according to Cockcroft-Gault formula Hemoglobin >9 g/dL Absolute neutrophil count ≥1.5 x10^9/L Platelet count ≥75 x10^9/L Able to provide informed consent Acceptable candidate for curative intent radiotherapy and Cemiplimab immunotherapy, in opinion of radiation and medical oncologist, respectively Life expectancy >18 months Exclusion Criteria: Primary tumor originating on the mucosal (non-hair bearing) lip or nose, anogenital (penis, scrotum, vulva, perianal) area Iatrogenic immunosuppression (>prednisone 10 mg/day or equivalent within 14 days of initiation of treatment) Women of child bearing potential unwilling or unable to use effective contraception while receiving treatment with cemiplimab and for 4 months thereafter Distant metastases Clinically significant autoimmune disease that requires iatrogenic immunosuppression o For example, severe rheumatoid arthritis requiring disease modifying antirheumatic drugs, such as methotrexate Current or previous hematopoietic malignancy (leukemia, lymphoma) Prior allogeneic transplant of solid organ or bone marrow Concurrent malignancies with >10% risk of metastasis or death within 2 years Prior aPD1 immunotherapy or PI3Kδ inhibitor use Prior radiotherapy for the cutaneous squamous cell carcinoma requiring treatment Other ongoing cancer therapy o Adjuvant endocrine therapy is permitted for patients with prostate or breast cancer Uncontrolled HIV or infectious hepatitis (viral load detectable in patient with known infection) Pregnancy or breastfeeding Comorbid or diagnostic abnormalities within the last year that would interfere with interpretation of study results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC<br>Participants have locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC | Drug: Cemiplimab<br>* Participants will undergo baseline imaging, followed by two doses of neoadjuvant cemiplimab at a dose of 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days). Then, participants will receive concurrent cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) concurrently with RT to 70 Gy in 35 fractions over 7 weeks. Thereafter, participants will receive 38 weeks of cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) for a cumulative total of 12 months of cemiplimab.<br>Radiation: Radiotherapy<br>* Participants will receive radiotherapy to 70 Gy in 35 fractions over 7 weeks concurrently with cemiplimab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | The primary endpoint for this study is disease free survival at 18 months (week 78 +/- 3 weeks) after starting cemiplimab. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin cancer, squamous cell carcinoma, locally advanced squamous cell carcinoma, Cutaneous Squamous Cell Carcinoma, Locally Advanced Squamous Cell Carcinoma of the Skin, Locally Advanced Cutaneous Squamous Cell Carcinoma, Locally Advanced Skin Squamous Cell Carcinoma, cemiplimab, RAMPART, 22-090, Memorial Sloan Kettering Cancer Center