Trial Title:
Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer
NCT ID:
NCT06568172
Condition:
Recurrent Cutaneous Squamous Cell Carcinoma of the Head and Neck
Recurrent Skin Squamous Cell Carcinoma
Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck
Resectable Skin Squamous Cell Carcinoma
Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Recurrence
Cemiplimab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Masking description:
A central review of 40% of patients who experience a recurrence or progression that is
considered a primary endpoint event will be conducted once the number of events for the
primary endpoint has been reached. Each case will be reviewed by two independent
reviewers who are blinded to the patient's assigned treatment arm.
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood and/or plasma
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Cemiplimab
Description:
Given IV
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
Cemiplimab RWLC
Other name:
Cemiplimab-rwlc
Other name:
Libtayo
Other name:
REGN 2810
Other name:
REGN-2810
Other name:
REGN2810
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT and/or PET/CT
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Radiation
Intervention name:
Image Guided Radiation Therapy
Description:
Undergo IGRT
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
IGRT
Other name:
image-guided radiation therapy
Other name:
Image-Guided Radiotherapy
Intervention type:
Radiation
Intervention name:
Intensity-Modulated Radiation Therapy
Description:
Undergo IMRT
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
IMRT
Other name:
Intensity modulated radiation therapy (procedure)
Other name:
Intensity Modulated RT
Other name:
Intensity-Modulated Radiotherapy
Other name:
Radiation, Intensity-Modulated Radiotherapy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm 1 (surgery, radiation)
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Intervention type:
Procedure
Intervention name:
Surgical Procedure
Description:
Undergo surgery per SOC
Arm group label:
Arm 1 (surgery, radiation)
Other name:
Operation
Other name:
Surgery
Other name:
Surgery Type
Other name:
Surgery, NOS
Other name:
Surgical
Other name:
Surgical Intervention
Other name:
Surgical Interventions
Other name:
Surgical Procedures
Other name:
Type of Surgery
Intervention type:
Procedure
Intervention name:
Surgical Procedure
Description:
Undergo response-adaptive surgery
Arm group label:
Arm 2 (cemiplimab, surgery, radiation)
Other name:
Operation
Other name:
Surgery
Other name:
Surgery Type
Other name:
Surgery, NOS
Other name:
Surgical
Other name:
Surgical Intervention
Other name:
Surgical Interventions
Other name:
Surgical Procedures
Other name:
Type of Surgery
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 disease-free survival (DFS) between arms. II. To compare overall survival
(OS) between arms. III. To compare adverse events (Common Terminology Criteria for
Adverse Events [CTCAE] version [v]5.0) between arms.
IV. 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 compare patterns of failure between arms. IV. To
compare pathologic measurements of lymph node yield between arms. V. To compare primary
tumor specimen dimensions and volume between arms. VI. To compare utilization of adjuvant
radiation 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 84 days 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 on study, 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 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 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 on study, and CT and/or MRI 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 6 and 12 months
post-surgery then every 3 months for 2 years, every 6 months in year 3, and then annually
thereafter.
Criteria for 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
- 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)
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCL)
> 30mL/min by the Cockcroft-Gault formula
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (not applicable to
patients with known Gilbert's syndrome)
- 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 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
- No history of interstitial lung disease (eg, idiopathic pulmonary fibrosis,
organizing pneumonia)
- No active, noninfectious pneumonitis requiring immune-suppressive therapy
- No active tuberculosis
- 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 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
January 9, 2025
Completion date:
August 14, 2031
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06568172
