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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05574101

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Locally Advanced Skin Squamous Cell Carcinoma	Drug: Cemiplimab Radiation: Radiotherapy	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 6, 2022

Anticipated Primary Completion Date :

Oct 6, 2024

Anticipated Study Completion Date :

Oct 6, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants with locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC Participants have locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC	Drug: Cemiplimab 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. Radiation: Radiotherapy Participants will receive radiotherapy to 70 Gy in 35 fractions over 7 weeks concurrently with cemiplimab

Arm

Intervention/Treatment

Experimental: Participants with locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC

Participants have locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC

Drug: Cemiplimab

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.

Radiation: Radiotherapy

Participants will receive radiotherapy to 70 Gy in 35 fractions over 7 weeks concurrently with cemiplimab

Outcome Measures

Primary Outcome Measures

Disease Free Survival [18 months]
The primary endpoint for this study is disease free survival at 18 months (week 78 +/- 3 weeks) after starting cemiplimab.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado (Data Collection Only)	Aurora	Colorado	United States	80045
2	Moffitt Cancer Center (Data Collection Only)	Tampa	Florida	United States	33612
3	Memorial Sloan Kettering Cancer Center at Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey	United States	07920
4	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey	United States	07748
5	Memorial Sloan Kettering Bergen (All protocol activities)	Montvale	New Jersey	United States	07645
6	Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities)	Commack	New York	United States	11725
7	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York	United States	10604
8	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York	United States	10065
9	Memorial Sloan Kettering Nassau (All protocol activities)	Rockville Centre	New York	United States	11553
10	Cleveland Clinic (Data Collection Only)	Cleveland	Ohio	United States	44195
11	Fox Chase Cancer Center (Data Collection Only)	Philadelphia	Pennsylvania	United States	19111
12	University of Washington (Data Collection Only)	Seattle	Washington	United States	98109