Trials / Recruiting

RecruitingNCT06568172

Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer

Randomized Phase III Trial of Neoadjuvant Immunotherapy With Response-Adapted Treatment Versus Standard-of-Care Treatment for Resectable Stage III/IV Cutaneous Squamous Cell Carcinoma (C-PRE)

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Enrollment: 420 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of adding cemiplimab to standard therapy (surgery with or without radiation) versus standard therapy alone in treating patients with stage III/IV squamous cell skin cancer that is able to be removed by surgery (resectable) and that may have come back after a period of improvement (recurrent). The usual treatment for patients with resectable squamous cell skin cancer is the removal of the cancerous tissue (surgery) with or without radiation, which uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cemiplimab has been approved for the treatment of skin cancer that has spread or that cannot be removed by surgery, but it has not been approved for the treatment of skin cancer than can be removed by surgery. Adding cemiplimab to the usual treatment of surgery with or without radiation may be more effective in treating patients with stage III/IV resectable squamous cell skin cancer than the usual treatment alone.

Detailed description

PRIMARY OBJECTIVE: I. To determine if neoadjuvant immunotherapy combined with response-adapted oncologic surgery improves site-reported event-free survival (EFS) compared to standard-of-care surgery in resectable stage III/IV cutaneous squamous cell carcinoma (CSCC). SECONDARY OBJECTIVES: I. To compare utilization of adjuvant radiation between arms. II. To compare disease-free survival (DFS) between arms. III. To compare overall survival (OS) between arms. IV. To compare adverse events (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0) between arms. V. To assess pathologic complete response in arm 2. PATIENT-REPORTED OUTCOMES: I. Compare changes in patient reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) at 1, 6, and 12 months after surgery between treatment arms. (Primary objective) II. To compare patient reported symptoms functioning, and quality of life, as measured by the Cutaneous Squamous Cell Carcinoma NeoAdjuvant, Adjuvant and Perioperative 32 question scale (CSCC NAAP-32), Patient Reported Outcomes Measurement Information System (PROMIS)-Short Form (SF)-Anxiety, PROMIS-SF-Fatigue, and EuroQol-5D (EQ-5D), between arms at 1, 6, and 12 months after surgery. III. Develop a scoring algorithm and validate the CSCC-NAAP-32 for use in this patient population. EXPLORATORY OBJECTIVES: I. To compare disease-specific survival (DSS) between arms. II. To correlate pathologic response with DFS in arm 2. III. To assess overall response rate (ORR) in arm 2. IV. To compare patterns of failure between arms. V. To compare pathologic measurements of lymph node yield between arms. VI. To compare primary tumor specimen dimensions and volume between arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 6-12 weeks of surgery, patients may undergo image-guided radiation therapy (IGRT) with intensity modulated radiation therapy (IMRT) for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT prior to treatment, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study. ARM 2: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo response-adaptive surgery 21 days after last dose of cemiplimab. Starting within 12 weeks of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Starting within 6 weeks of completion of surgery or radiation therapy (if indicated), patients without pathologic complete response (pCR) receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET/CT prior to treatment, and CT and/or MRI on study and during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study. After completion of study treatment, patients are followed up at 1, 6, and 12 months post-surgery then every 3 months for 2 years, every 6 months in year 3, and then annually thereafter.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood and/or plasma
BIOLOGICAL	Cemiplimab	Given IV
PROCEDURE	Computed Tomography	Undergo CT and/or PET/CT
RADIATION	Image Guided Radiation Therapy	Undergo IGRT
RADIATION	Intensity-Modulated Radiation Therapy	Undergo IMRT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Surgical Procedure	Undergo surgery per SOC
PROCEDURE	Surgical Procedure	Undergo response-adaptive surgery

Timeline

Start date: 2025-02-18
Primary completion: 2031-08-14
Completion: 2031-08-14
First posted: 2024-08-23
Last updated: 2026-04-16

Locations

200 sites across 3 countries: United States, Australia, Canada

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06568172. Inclusion in this directory is not an endorsement.