Trials / Recruiting
RecruitingNCT07281417
Testing the Addition of Cemiplimab (REGN2810) to Chemotherapy Treatment Given Prior to Surgery in Patients With Sinonasal Squamous Cell Carcinoma
Neoadjuvant Chemotherapy With or Without Cemiplimab (REGN2810) in Sinonasal Squamous Cell Carcinoma: A Randomized Phase 2 Study
- Status
- Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 108 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase II trial compares the effect of chemotherapy (carboplatin and paclitaxel) with versus without cemiplimab given before surgery (neoadjuvant) in patients with sinonasal squamous cell cancer. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. 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. The usual approach for patients with sinonasal squamous cell cancer is surgery followed by radiation therapy, with or without chemotherapy. Recently, some patients have also been treated with neoadjuvant chemotherapy before surgery. Adding cemiplimab to chemotherapy before surgery may be more effective at stopping the cancer from growing or spreading, compared to chemotherapy alone.
Detailed description
PRIMARY OBJECTIVE: I. To assess whether neoadjuvant therapy (NAT) with cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) results in improved event free survival (EFS) compared to carboplatin/paclitaxel (Arm 2) in participants with sinonasal squamous cell carcinoma (SNSCC). SECONDARY OBJECTIVES: I. To compare objective response rate (ORR) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and neoadjuvant carboplatin/paclitaxel (Arm 2) and to historical standard of care (SOC) in participants with SNSCC. II. To compare overall survival (OS) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and carboplatin/paclitaxel (Arm 2) and to historical SOC in participants with SNSCC. III. To characterize toxicity with NAT in SNSCC. IV. To measure changes in T-cell clonality/diversity using ribonucleic acid (RNA) sequencing (RNAseq) and correlate with NAT response and EFS. V. To evaluate organ preservation (orbital and skull base) rate with NAT in SNSCC. CORRELATIVE OBJECTIVES: I. To correlate human papillomavirus (HPV) status with ORR and OS after NAT. II. To correlate combined positive score (CPS) for PD-L1 expression with OS and EFS. III. To measure the kinetics of circulating tumor DNA (ctDNA) pre- and post-NAT and correlate with ORR and OS after NAT. IV. To conduct DNA sequencing on pre-treatment tumor biopsies to determine whether features of the tumor genomic landscape are associated with response to NAT. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: NAT: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle, carboplatin IV over 30 minutes on day 1 of each cycle, and paclitaxel IV over 180 minutes on day 1 of each cycle. Cycles repeat every 21 days (3 weeks) for up to 2 cycles (6 weeks) in the absence of disease progression or unacceptable toxicity. At the discretion of the investigator, patients may alternatively receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes weekly during the 2, 3-week cycles. Up to 14 days after completion of NAT, patients are evaluated for response and proceed to definitive therapy. DEFINITIVE THERAPY: Patients with complete response (CR) or partial response (PR) receive concurrent SOC chemoradiotherapy (CRT). Patients with stable disease (SD) or progressive disease (PD) undergo surgery within 6 weeks of completion of NAT followed by SOC adjuvant therapy. ADJUVANT THERAPY: Within 4-6 weeks of surgery, patients undergo radiation therapy (RT) once daily, 5 days per week for a total of 30 fractions over 6 weeks and receive cisplatin or carboplatin weekly during RT. Patients also undergo magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT), CT, and collection of blood samples throughout the trial. Patients may undergo biopsy pre-treatment and/or on study. ARM 2: NAT: Patients receive carboplatin IV over 30 minutes on day 1 of each cycle and paclitaxel IV over 180 minutes on day 1 of each cycle. Cycles repeat every 21 days (3 weeks) for up to 2 cycles (6 weeks) in the absence of disease progression or unacceptable toxicity. At the discretion of the investigator, patients may alternatively receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes weekly during the 2, 3-week cycles. Up to 14 days after completion of NAT, patients are evaluated for response and proceed to definitive therapy. DEFINITIVE THERAPY: Patients with CR or PR receive concurrent SOC CRT. Patients with SD or PD undergo surgery within 6 weeks of completion of NAT followed by SOC adjuvant therapy. ADJUVANT THERAPY: Within 4-6 weeks of surgery, patients undergo RT once daily, 5 days per week for a total of 30 fractions over 6 weeks and receive cisplatin or carboplatin weekly during RT. Patients also undergo MRI, PET/CT, CT, and collection of blood samples throughout the trial. Patients may undergo biopsy pre-treatment and/or on study. After completion of definitive therapy, patients are followed up at 3, 9, 15, 21, and 27 months and then every 12 months for an additional 3 years (5 years total follow up).
Conditions
- Sinonasal Squamous Cell Carcinoma
- Stage III Sinonasal Cancer AJCC v8
- Stage IVA Sinonasal Cancer AJCC v8
- Stage IVB Sinonasal Cancer AJCC v8
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biopsy Procedure | Undergo biopsy |
| PROCEDURE | Biospecimen Collection | Undergo collection of blood samples |
| DRUG | Carboplatin | Given IV |
| DRUG | Carboplatin | Given carboplatin |
| BIOLOGICAL | Cemiplimab | Given IV |
| OTHER | Chemoradiotherapy | Undergo SOC CRT |
| DRUG | Cisplatin | Given cisplatin |
| PROCEDURE | Computed Tomography | Undergo PET/CT and CT |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| DRUG | Paclitaxel | Given IV |
| PROCEDURE | Positron Emission Tomography | Undergo PET/CT |
| RADIATION | Radiation Therapy | Undergo radiation therapy |
| PROCEDURE | Surgical Procedure | Undergo surgery |
Timeline
- Start date
- 2026-11-24
- Primary completion
- 2030-12-16
- Completion
- 2030-12-16
- First posted
- 2025-12-15
- Last updated
- 2026-04-13
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT07281417. Inclusion in this directory is not an endorsement.