NCT05085496

Radiotherapy in Combination With Atezolizumab in Locally Advanced Borderline Resectable or Unresectable Cutaneous SCC

Phase I Trial of Radiotherapy in Combination With Atezolizumab in Borderline Resectable and Unresectable Cutaneous Squamous Cell Carcinoma(cSCC)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety and side effects radiotherapy in combination with atezolizumab in treating patients with cutaneous squamous cell cancer that has spread to nearby tissue or lymph nodes (locally advanced) and can be removed from surgery (resectable) or cannot be remove by surgery (unresectable). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiotherapy in combination with atezolizumab may help improve outcomes for remission (cancer that is under control) than taking either treatment separately.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety profile of combination of atezolizumab + radiation therapy (RT) in borderline resectable or unresectable cutaneous squamous cell carcinoma (cSCC). SECONDARY OBJECTIVES: I. Determine pathologic response after neoadjuvant atezolizumab + RT. II. Determine clinical response (via imaging and clinical exam) postoperatively (if surgically resectable) or at post-treatment biopsy (if not surgically resectable), and 3 months following the completion of surgery or RT (if not surgically resectable). III. Define the toxicity profile associated with the treatment protocol. IV. Assess short-term quality-of-life associated with the treatment protocol. EXPLORATORY OBJECTIVES: I. To compare immune checkpoint molecule (e.g. PD1, PD-L1, TIM3, TIGIT, etc.) expression intensity within tumor cells and immune cells in the tumor microenvironment, as well as immune cell subset infiltration patterns including T cells before and after atezolizumab + stereotactic body radiation therapy (SBRT) by multiplex immunohistochemistry (or immunofluorescence). II. To evaluate the impact of tumor molecular features on immune response and treatment outcome using next generation targeted deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing of pre-treatment tumor tissue. III. To compare changes in circulating immune cell subsets in peripheral blood by RNA-based T-cell receptor (TCR)-sequencing and immunophenotyping by flow cytometry (or immunophenotyping by single-cell RNA sequencing), and correlate changes with response, clinical outcomes, and toxicity. IV. To evaluate circulating tumor DNA (ctDNA) levels before start of treatment and immediately prior to surgery/repeat biopsy. OUTLINE: Patients undergo SBRT on days 1, 3, 5, 7, and 9 of cycle 1. Beginning 1-2 days after SBRT, patients also receive atezolizumab intravenously (IV) on day 1. Treatment repeats every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up every 12 weeks for 24 months.

Conditions

• Locally Advanced Skin Squamous Cell Carcinoma
• Resectable Skin Squamous Cell Carcinoma
• Unresectable Skin Squamous Cell Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Atezolizumab	Given IV
RADIATION	Stereotactic Body Radiation Therapy	Undergo SBRT

Timeline

• Start date: 2022-04-19
• Primary completion: 2027-09-10
• Completion: 2027-09-10
• First posted: 2021-10-20
• Last updated: 2026-01-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study