Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
A database of clinical trials and their results from Australia, New Zealand, and other countries.
account_circle
Log in
to register or update your trial
search
Search for trials
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06568172
Registration number
NCT06568172
Ethics application status
Date submitted
22/08/2024
Date registered
23/08/2024
Date last updated
12/09/2025
Titles & IDs
Public title
Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer
Query!
Scientific title
Randomized Phase III Trial of Perioperative Immunotherapy With Response-Adapted Treatment Versus Standard-of-Care Treatment for Resectable Stage III/IV Cutaneous Squamous Cell Carcinoma
Query!
Secondary ID [1]
0
0
NCI-2024-03425
Query!
Secondary ID [2]
0
0
NCI-2024-03425
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Recurrent Head and Neck Cutaneous Squamous Cell Carcinoma
0
0
Query!
Recurrent Skin Squamous Cell Carcinoma
0
0
Query!
Resectable Head and Neck Cutaneous Squamous Cell Carcinoma
0
0
Query!
Resectable Skin Squamous Cell Carcinoma
0
0
Query!
Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
0
0
Query!
Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
0
0
Query!
Condition category
Condition code
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Other - Cemiplimab
Treatment: Surgery - Computed Tomography
Treatment: Other - Image Guided Radiation Therapy
Treatment: Other - Intensity-Modulated Radiation Therapy
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Positron Emission Tomography
Other interventions - Questionnaire Administration
Treatment: Surgery - Surgical Procedure
Treatment: Surgery - Surgical Procedure
Active comparator: Arm 1 (surgery, radiation) - Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 84 days of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo CT, MRI, and/or PET/CT on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.
Experimental: Arm 2 (cemiplimab, surgery, radiation) - Patients receive cemiplimab 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 84 days 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 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 on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.
Treatment: Surgery: Biospecimen Collection
Undergo collection of blood and/or plasma
Treatment: Other: Cemiplimab
Given IV
Treatment: Surgery: Computed Tomography
Undergo CT and/or PET/CT
Treatment: Other: Image Guided Radiation Therapy
Undergo IGRT
Treatment: Other: Intensity-Modulated Radiation Therapy
Undergo IMRT
Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI
Treatment: Surgery: Positron Emission Tomography
Undergo PET/CT
Other interventions: Questionnaire Administration
Ancillary studies
Treatment: Surgery: Surgical Procedure
Undergo surgery per SOC
Treatment: Surgery: Surgical Procedure
Undergo response-adaptive surgery
Query!
Intervention code [1]
0
0
Treatment: Surgery
Query!
Intervention code [2]
0
0
Treatment: Other
Query!
Intervention code [3]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Event-free survival (EFS)
Query!
Assessment method [1]
0
0
Defined as the time from randomization to any of the following events: progression of disease that precludes surgery, toxic effects related to treatment that preclude surgery, inability to resect all gross disease), disease recurrence (local, regional, or distant) after surgery (or after radiographic complete response), disease progression after radiographic partial response or stable disease without surgery (or biopsy, as applicable), or death due to any cause, whichever occurs first. EFS rates will be estimated using the Kaplan-Meier method, and the stratified log-rank test will be used to assess whether perioperative immunotherapy (neoadjuvant/adjuvant) with response-adapted oncologic surgery improves EFS as recorded by the site compared to standard-of-care surgery in resectable stage III/IV cutaneous squamous cell carcinoma (CSCC).
Query!
Timepoint [1]
0
0
Up to 6 years
Query!
Secondary outcome [1]
0
0
Disease-free survival (DFS)
Query!
Assessment method [1]
0
0
DFS will use the same analytic methods as EFS.
Query!
Timepoint [1]
0
0
From randomization to recurrent or death, assessed up to 6 years
Query!
Secondary outcome [2]
0
0
Overall survival (OS)
Query!
Assessment method [2]
0
0
OS will use the same analytic methods as EFS.
Query!
Timepoint [2]
0
0
From randomization to death, assessed up to 6 years
Query!
Secondary outcome [3]
0
0
Incidence of adverse events
Query!
Assessment method [3]
0
0
Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events version 5.0. Counts and frequencies of all AEs by grade will be provided by each treatment arm. For the experimental arm, AEs will be summarized for each treatment phase (neoadjuvant, adjuvant, and post-treatment \[after adjuvant\]). Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The proportion of patients with at least one grade 3 or higher AE, serious AEs, AEs leading to discontinuation or death will be reported for each treatment arm. These analyses will be descriptive.
Query!
Timepoint [3]
0
0
At 30 days and then up to 6 years
Query!
Secondary outcome [4]
0
0
Pathologic complete response
Query!
Assessment method [4]
0
0
Site-reported pathologic response will be assessed using the following categories: pathological complete, major, and partial response, no pathological response (i.e., no complete, major, or partial response), and no pathological evaluation. Pathological responses at 1 and 2 years will be summarized using frequencies and percentages and tested using a chi-square test at a two-sided 5% significance level.
Query!
Timepoint [4]
0
0
At 1 and 2 years
Query!
Eligibility
Key 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
* 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 squamous cell carcinoma (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 (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
* 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
* 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 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 transplant)
* No active, known, or suspected autoimmune disease
* Active or known disease is defined as:
* Requiring higher than physiologic steroid levels (> 10mg prednisone/day or equivalent) or
* Requiring disease-modifying agents or
* Ongoing or recent (within 5 years prior to registration) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs)
* NOTES:
* Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:
* Patients who require a brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
* Patients with type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Physiologic replacement doses = 10 mg prednisone/day or equivalent allowed, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted
* Patients with the following immunosuppressed conditions are eligible to enroll:
* Patients with HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible
* Patients with chronic lymphocytic leukemia (CLL) with no history of anti-CLL therapy within 6 months prior to registration are eligible
* No history of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia)
* No active, noninfectious pneumonitis requiring immune-suppressive therapy
* No active tuberculosis
* No live vaccines within 28 days prior to registration
* No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent (or any of its excipients)
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people assessing the outcomes
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
18/02/2025
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
14/08/2031
Query!
Actual
Query!
Sample size
Target
420
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Peter MacCallum Cancer Centre - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3000 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Connecticut
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Delaware
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Georgia
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Illinois
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Indiana
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Kansas
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Kentucky
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Louisiana
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Michigan
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Missouri
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Nebraska
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
New Hampshire
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
New Jersey
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
New Mexico
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
New York
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
North Carolina
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Ohio
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Oklahoma
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Pennsylvania
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
South Carolina
Query!
Country [24]
0
0
United States of America
Query!
State/province [24]
0
0
Tennessee
Query!
Country [25]
0
0
United States of America
Query!
State/province [25]
0
0
Texas
Query!
Country [26]
0
0
United States of America
Query!
State/province [26]
0
0
Utah
Query!
Country [27]
0
0
United States of America
Query!
State/province [27]
0
0
Vermont
Query!
Country [28]
0
0
United States of America
Query!
State/province [28]
0
0
Virginia
Query!
Country [29]
0
0
United States of America
Query!
State/province [29]
0
0
Wisconsin
Query!
Funding & Sponsors
Primary sponsor type
Government body
Query!
Name
National Cancer Institute (NCI)
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief 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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT06568172
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Neil D Gross
Query!
Address
0
0
NRG Oncology
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
Query!
What data in particular will be shared?
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Query!
When will data be available (start and end dates)?
Query!
Available to whom?
Query!
Available for what types of analyses?
Query!
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06568172
Download to PDF