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)

Testing a New Treatment for Advanced Skin Cancer

NCT: NCT06568172 · Status: RECRUITING · Phase: Phase 3 · Sponsor: National Cancer Institute (NCI) · Started: 2025-02-18 · Est. Completion: 2031-08-14

Plain English Summary

Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Eyelid Squamous Cell Carcinoma, Recurrent Eyelid Squamous Cell Carcinoma, Recurrent Skin Acantholytic Squamous Cell Carcinoma, Recurrent Skin Clear Cell Squamous Cell Carcinoma, Recurrent Skin Lymphoepithelial Carcinoma, Recurrent Skin Spindle Cell Squamous Cell Carcinoma, Recurrent Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation, Resectable Eyelid Squamous Cell Carcinoma, Resectable Skin Acantholytic Squamous Cell Carcinoma, Resectable Skin Clear Cell Squamous Cell Carcinoma. This trial compares a new treatment with the usual surgery for advanced skin cancer. It's for people with resectable or recurrent squamous cell skin cancer in the head and neck region. Participants will get either surgery alone or surgery plus a new drug called cemiplimab. Patients will be monitored for up to 6 years to see how well the treatments work. The trial aims to enroll 420 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients have invasive squamous cell skin cancer in the head and neck region. Patients must be at least 18 years old and in good health. Those with other types of cancer or who have had previous treatments are not eligible. People with active infections or a history of organ transplants are also not eligible. This trial is studying Eyelid Squamous Cell Carcinoma, Recurrent Eyelid Squamous Cell Carcinoma, Recurrent Skin Acantholytic Squamous Cell Carcinoma, Recurrent Skin Clear Cell Squamous Cell Carcinoma, Recurrent Skin Lymphoepithelial Carcinoma, Recurrent Skin Spindle Cell Squamous Cell Carcinoma, Recurrent Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation, Resectable Eyelid Squamous Cell Carcinoma, Resectable Skin Acantholytic Squamous Cell Carcinoma, Resectable Skin Clear Cell Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients stay free from cancer recurrence or death. The specific primary outcome measures are: Event-free survival (EFS) (Up to 6 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by testing a new immunotherapy drug for advanced skin cancer. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Eyelid Squamous Cell Carcinoma, Recurrent Eyelid Squamous Cell Carcinoma, Recurrent Skin Acantholytic Squamous Cell Carcinoma, Recurrent Skin Clear Cell Squamous Cell Carcinoma, Recurrent Skin Lymphoepithelial Carcinoma, Recurrent Skin Spindle Cell Squamous Cell Carcinoma, Recurrent Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation, Resectable Eyelid Squamous Cell Carcinoma, Resectable Skin Acantholytic Squamous Cell Carcinoma, Resectable Skin Clear Cell Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

The market for skin cancer treatments is large, and this trial could lead to a new approved treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have any of the eligible types of skin cancer in the head and neck region. You will need to have a tumor that can be removed with surgery and no distant metastasis. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

  • Study Type: INTERVENTIONAL
  • Allocation: RANDOMIZED
  • Model: PARALLEL
  • Masking: SINGLE
  • Enrollment: 420 participants

Interventions

  • 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

Primary Outcomes

  • Event-free survival (EFS) (Up to 6 years)

Secondary Outcomes

  • Utilization of adjuvant radiation (Up to 6 years)
  • Disease-free survival (DFS) (From randomization to recurrent or death, assessed up to 6 years)
  • Overall survival (OS) (From randomization to death, assessed up to 6 years)
  • Incidence of adverse events (At 30 days and then up to 6 years)
  • Pathologic complete response (At 1 and 2 years)

Full Eligibility Criteria

Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of invasive cutaneous squamous cell carcinoma (CSCC) or regional lymph node or in-transit metastasis of CSCC

  * The following CSCC subtypes are eligible according to World Health Organization (WHO) classification if the predominant histology is confirmed CSCC.

    * Spindle cell squamous cell carcinoma (SCC)
    * Squamous cell carcinoma with sarcomatoid differentiation
    * Acantholytic SCC
    * Clear cell SCC
    * Lymphoepithelial carcinoma

      * Note: Keratoacanthoma SCC and Verrucous SCC subtypes are not eligible.
  * For patients with regional metastasis without a primary tumor at screening: a clinical history of CSCC that drains to the involved regional lymph nodes or in-transit metastases in question is required

    * For example, a parotid mass shown to be SCC by cytologic analysis of a fine needle aspirate in a patient with a clinical history of CSCC on the ipsilateral scalp would be eligible
  * For patients with regional metastases without a primary tumor and an ambiguous clinical history: tumor genomic sequencing suggesting a primary tumor of cutaneous origin would be acceptable evidence to establish eligibility
  * NOTE: Tumor genomic sequencing is not required to determine eligibility, but may be part of the routine evaluation of patients with cancers of unknown primary at some institutions. For example, a parotid mass shown to be SCC by cytologic analysis of fine needle aspirate without a primary tumor and an ambiguous clinical history, but with a tumor genomic sequencing assay demonstrating a high tumor mutation burden (≥ 10 mutations/Mb) and/or a high fraction of ultraviolet (UV) related mutations (\> 50% of mutations \[cytosine (C)/thymine (T)\]C \> T or CC \> TT) and/or the presence of "signature 7" mutations would be eligible (Chang 2021)
* Previously untreated or recurrent CSCC
* Clinical American Joint Committee on Cancer (AJCC) 8th Edition (eyelid, head and neck sites) or Union for International Cancer Control (UICC) (non-head and neck sites) stage III or IV
* Primary tumor site must be in the head and neck cutaneous region, other non-head and neck cutaneous regions, or eyelid cutaneous region
* No mucosal squamous cell carcinoma (vermillion lip, nasal, oral, sinonasal, conjunctival, anogenital)
* Tumor must be resectable with curative intent. Note: Tumor with bony skull base invasion and/or skull base foramen involvement (T4b) is not eligible. (Patients with T4b eyelid tumors using UICC Staging, and not involving the brain, are eligible.)
* At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No definitive clinical or radiologic evidence of distant metastatic disease (M1), visceral and/or distant nodal disease
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Not pregnant and not nursing

  * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
* Platelets ≥ 75,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
* Creatinine clearance (CrCL) \> 30mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (NOTE: For patients with Gilbert's syndrome, total bilirubin ≤ 3 x ULN. Gilbert's syndrome must be documented appropriately as past medical history.)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
* No prior systemic therapy for the study cancer (including patients currently receiving immunotherapy for a separate malignancy)
* No prior radiotherapy to the region of the study cancer that would result in cumulative doses of radiation to organs at risk for radiation injury that exceed protocol limitations
* No history of myocardial infarction/unstable angina within the last 6 months
* New York Heart Association functional classification IIb or better (New York Heart Association \[NYHA\] functional classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification)
* No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
* No history of allogeneic stem cell transplantation, or autologous stem cell transplantation
* No history of a solid organ transplant (other than corneal

Trial Locations

  • University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
  • Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
  • Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
  • Tower Cancer Research Foundation, Beverly Hills, California, United States
  • City of Hope Comprehensive Cancer Center, Duarte, California, United States
  • UC San Diego Health System - Encinitas, Encinitas, California, United States
  • City of Hope at Irvine Lennar, Irvine, California, United States
  • UC San Diego Moores Cancer Center, La Jolla, California, United States
  • City of Hope Antelope Valley, Lancaster, California, United States
  • The Angeles Clinic and Research Institute - West Los Angeles Office, Los Angeles, California, United States
  • ...and 10 more locations

Frequently Asked Questions

What is clinical trial NCT06568172?

NCT06568172 is a Phase 3 INTERVENTIONAL study titled "Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer." It is currently recruiting and is sponsored by National Cancer Institute (NCI). The trial targets enrollment of 420 participants.

What conditions does NCT06568172 study?

This trial investigates treatments for Eyelid Squamous Cell Carcinoma, Recurrent Eyelid Squamous Cell Carcinoma, Recurrent Skin Acantholytic Squamous Cell Carcinoma, Recurrent Skin Clear Cell Squamous Cell Carcinoma, Recurrent Skin Lymphoepithelial Carcinoma, Recurrent Skin Spindle Cell Squamous Cell Carcinoma, Recurrent Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation, Resectable Eyelid Squamous Cell Carcinoma, Resectable Skin Acantholytic Squamous Cell Carcinoma, Resectable Skin Clear Cell Squamous Cell Carcinoma. The primary condition under study is Eyelid Squamous Cell Carcinoma.

What treatments are being tested in NCT06568172?

The interventions being studied include: Biospecimen Collection (PROCEDURE), Cemiplimab (BIOLOGICAL), Computed Tomography (PROCEDURE), Image Guided Radiation Therapy (RADIATION), Intensity-Modulated Radiation Therapy (RADIATION). Undergo collection of blood and/or plasma

What does Phase 3 mean for NCT06568172?

Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.

What is the current status of NCT06568172?

This trial is currently "Recruiting." It started on 2025-02-18. The estimated completion date is 2031-08-14.

Who is sponsoring NCT06568172?

NCT06568172 is sponsored by National Cancer Institute (NCI). The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06568172?

The trial aims to enroll 420 participants. The trial is currently recruiting and accepting new participants.

How is NCT06568172 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs single masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.

What are the primary outcomes being measured in NCT06568172?

The primary outcome measures are: Event-free survival (EFS) (Up to 6 years). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06568172 being conducted?

This trial is being conducted at 20 sites, including Birmingham, Alabama; Gilbert, Arizona; Phoenix, Arizona; Beverly Hills, California and 16 more sites (United States).

Where can I find official information about NCT06568172?

The official record for NCT06568172 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06568172. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06568172 testing in simple terms?

This trial compares a new treatment with the usual surgery for advanced skin cancer. It's for people with resectable or recurrent squamous cell skin cancer in the head and neck region.

Why is this trial significant?

This trial aims to fill a treatment gap by testing a new immunotherapy drug for advanced skin cancer. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.

What are the potential risks of participating in NCT06568172?

Side effects may include fatigue, skin reactions, and flu-like symptoms. Serious side effects are rare but can include severe infections or allergic reactions. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06568172?

Ask your doctor if you have any of the eligible types of skin cancer in the head and neck region. You will need to have a tumor that can be removed with surgery and no distant metastasis. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06568172 signal from an investment perspective?

The market for skin cancer treatments is large, and this trial could lead to a new approved treatment. This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.

What happens if the treatment in this trial doesn't work?

Participants will get either surgery alone or surgery plus a new drug called cemiplimab. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.