De-escalation Radiation Strategy After NAC in Combination With ICI in LAHNSCC

Official title

The Exploratory Study of the Feasibility of De-escalating Radiation Strategy After NAC in Combination With Immunotherapy in LAHNSCC

Overview

This study is a single-arm exploratory study conducted in LAHNSCC. Eligible patients received two cycles of pembrolizumab immunotherapy in combination with albumin-bound paclitaxel and cisplatin induction chemotherapy, followed by definitive concurrent radiochemotherapy. Three months after the completion of radiotherapy, a follow-up examination was conducted, and salvage surgery or systemic therapy was performed as necessary based on the follow-up results.

Interventions

• Drug immunotherapy：pembrolizumab；chemo：albumin-bound paclitaxel and cisplatin
  The immunotherapy drug was pembrolizumab at a dose of 200 mg, administered on the first day of each cycle every 3 weeks. The induction chemotherapy regimen included albumin-bound paclitaxel at 260 mg/m2 and cisplatin at 75 mg/m2, given every 3 weeks, either concurrently with immunotherapy or on the second day.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: 1 year]

Secondary outcome measures (4)

• Overall survival (OS) [Time frame: 3-year]
• Clinical response rate [Time frame: 6 months]
• Safety(Grade 3-5 AE) [Time frame: 1-year]
• Quality of life [Time frame: 6 month and 1 year after the treatment]

Eligibility criteria

Inclusion criteria

• ≥18 years old, with medical decision-making capacity
• Signed informed consent
• ECOG score of 0-1
• Pathologically diagnosed with oral cancer, oropharyngeal cancer, laryngeal cancer, or hypopharyngeal cancer
• Exclusion of distant metastasis
• Clearly evaluable lesion (per RECIST 1.1 criteria)
• Expected life span ≥6 months
• Laboratory test results meet the following requirements: WBC ≥ 3×10\^9/L, ANC ≥ 2.0×10\^9/L, PLT ≥ 80×10\^9/L, Hb ≥ 80g/L (according to the normal standards of the central laboratory); Liver function: Total bilirubin, ALT, and AST all ≤ 1.5x UNL (upper normal limit); AST (SGOT)/ALT (SGPT) ≤ 2.5 x IULN (upper normal limit); Kidney function: Cr ≤ 1.5x UNL (upper normal limit), and creatinine clearance rate ≥ 60 ml/min (calculated using the Cockcroft and Gault formula); Thyroid function T3 and T4 within the normal range (hypothyroidism can be corrected with oral thyroid hormone supplementation); Heart function: All three cardiac enzymes and pro-BNP within the normal range, no history of heart attack; Adrenal function: Normal cortisol secretion function or correctable based on endocrine assessment
• HBV-infected patients with HBV-DNA copy numbers less than 500 IU/ml
• No history of other malignant tumors in the past 5 years (excluding basal cell carcinoma of the skin and thyroid cancer).

Exclusion criteria

• No indications for curative radiotherapy or contraindications to radiochemotherapy.
• Clinical factors identified by the investigator that could potentially affect the completion of the study protocol (such as bleeding, active infection, or mental factors).
• Patients requiring long-term maintenance steroid therapy (including oral and intravenous use); local use or inhalation can be included in the study.
• Previous history of autoimmune diseases or in the active phase of the disease \[including but not limited to inflammatory bowel disease (IBD), rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and its variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barré syndrome)\], vitiligo, and correctable endocrine deficiencies such as hypothyroidism and physiological cortisol deficiency can be included in the study and are not exclusion criteria.
• History of active tuberculosis or non-infectious pneumonia or any clinical evidence.
• Active phase of viral hepatitis, HBV DNA > 500 IU/ml.
• Acquired Immunodeficiency Syndrome (AIDS).
• Concurrent severe medical conditions (including heart diseases) with coexisting diseases or conditions affecting the patient's normal enrollment or safety during the study.
• Prior immunotherapy for other tumors.
• History of other malignant tumors within 5 years (excluding cured basal cell carcinoma of the skin or thyroid cancer).
• Pregnant or lactating women.
• Concurrently suffering from other malignant tumors.
• Cannot or unwilling to sign the informed consent form.
• Vaccination within 4 weeks.
• Allergic reaction to the investigational drug.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai

Identifiers

NCT: NCT06572514 · LAHNSCC-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗