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Back|NCT06568172Recruiting
Official Title

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)

Phase
Phase 3
Sponsor
National Cancer Institute (NCI)
Enrollment
420
Timeline
Feb 2025 → Aug 2031
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Pathologically (histologically or cytologically) proven diagnosis of invasive cutaneous squamous cell carcinoma (CSCC) or regional lymph node or in-transit metastasis of CSCC
  • 2The following CSCC subtypes are eligible according to World Health Organization (WHO) classification if the predominant histology is confirmed CSCC.
  • 3Spindle cell squamous cell carcinoma (SCC)
  • 4Squamous cell carcinoma with sarcomatoid differentiation
  • 5Acantholytic SCC
  • 6Clear cell SCC
  • 7Lymphoepithelial carcinoma
  • 8Note: Keratoacanthoma SCC and Verrucous SCC subtypes are not eligible.
  • 9For 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
  • 10For 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
  • 11For 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
  • 12NOTE: 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)
  • 13Previously untreated or recurrent CSCC
  • 14Clinical 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
  • 15Primary tumor site must be in the head and neck cutaneous region, other non-head and neck cutaneous regions, or eyelid cutaneous region
  • 16No mucosal squamous cell carcinoma (vermillion lip, nasal, oral, sinonasal, conjunctival, anogenital)
  • 17Tumor 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.)
  • 18At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • 19No definitive clinical or radiologic evidence of distant metastatic disease (M1), visceral and/or distant nodal disease
  • 20Age ≥ 18
  • 21Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • 22Not pregnant and not nursing
  • 23Negative 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
  • 24Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
  • 25Platelets ≥ 75,000 cells/mm\^3
  • 26Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
  • 27Creatinine clearance (CrCL) \> 30mL/min by the Cockcroft-Gault formula
  • 28Total 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.)
  • 29Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
  • 30No prior systemic therapy for the study cancer (including patients currently receiving immunotherapy for a separate malignancy)
  • 31No 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
  • 32No history of myocardial infarction/unstable angina within the last 6 months
  • 33New 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)
  • 34No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
  • 35No history of allogeneic stem cell transplantation, or autologous stem cell transplantation
  • 36No history of a solid organ transplant (other than corneal transplant)
  • 37No active, known, or suspected autoimmune disease
  • 38Active or known disease is defined as:
  • 39Requiring higher than physiologic steroid levels (\> 10mg prednisone/day or equivalent) or
  • 40Requiring disease-modifying agents or
  • 41Ongoing 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)
  • 42NOTES:
  • 43Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:
  • 44Patients who require a brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
  • 45Patients 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
  • 46Physiologic 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
  • 47Patients with the following immunosuppressed conditions are eligible to enroll:
  • 48Patients with HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible
  • 49Patients with chronic lymphocytic leukemia (CLL) with no history of anti-CLL therapy within 6 months prior to registration are eligible
  • 50No history of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia)
  • 51No active, noninfectious pneumonitis requiring immune-suppressive therapy
  • 52No active tuberculosis
  • 53No live vaccines within 28 days prior to registration
  • 54No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent (or any of its excipients)

Locations

172 sites participating in this study

Emory University Hospital Midtown

Atlanta, Georgia 30308

Recruiting

Jennifer Gross

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Jennifer Gross

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

Recruiting

Mehran Yusuf

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →