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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: immunotherapy：pembrolizumab；chemo：albumin-bound paclitaxel and cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yujie Wang, M.D.; Phone Number: 602400 +86 02164370045; Email: wyj12054@rjh.com.cn
• Study Contact Backup: Name: Yusheng Gao, M.D.; Phone Number: 602400 +86 02164370045; Email: gys11856@rjh.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Yunsheng Gao, M.D.; Phone Number: 602400 +86-021-64370045; Email: gys11856@rjh.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥18 years old, with medical decision-making capacity
2. Signed informed consent
3. ECOG score of 0-1
4. Pathologically diagnosed with oral cancer, oropharyngeal cancer, laryngeal cancer, or hypopharyngeal cancer
5. Exclusion of distant metastasis
6. Clearly evaluable lesion (per RECIST 1.1 criteria)
7. Expected life span ≥6 months
8. 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
9. HBV-infected patients with HBV-DNA copy numbers less than 500 IU/ml
10. No history of other malignant tumors in the past 5 years (excluding basal cell carcinoma of the skin and thyroid cancer).

Exclusion Criteria:

1. No indications for curative radiotherapy or contraindications to radiochemotherapy.
2. Clinical factors identified by the investigator that could potentially affect the completion of the study protocol (such as bleeding, active infection, or mental factors).
3. Patients requiring long-term maintenance steroid therapy (including oral and intravenous use); local use or inhalation can be included in the study.
4. 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.
5. History of active tuberculosis or non-infectious pneumonia or any clinical evidence.
6. Active phase of viral hepatitis, HBV DNA > 500 IU/ml.
7. Acquired Immunodeficiency Syndrome (AIDS).
8. Concurrent severe medical conditions (including heart diseases) with coexisting diseases or conditions affecting the patient's normal enrollment or safety during the study.
9. Prior immunotherapy for other tumors.
10. History of other malignant tumors within 5 years (excluding cured basal cell carcinoma of the skin or thyroid cancer).
11. Pregnant or lactating women.
12. Concurrently suffering from other malignant tumors.
13. Cannot or unwilling to sign the informed consent form.
14. Vaccination within 4 weeks.
15. Allergic reaction to the investigational drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: experimental arm; Eligible patients received two cycles of pembrolizumab immunotherapy in combination with albumin-bound paclitaxel and cisplatin induction chemotherapy, followed by definitive concurrent radiochemotherapy.

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.; Other Names: definitive radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) (local-regional recurrence) is defined as the time from enrollment to the occurrence of local or regional lymph node recurrence or death for any reason.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival is defined as the time from enrollment to death for any reason	3-year
Clinical response rate	Clinical response is defined as the radiological evaluation of tumor regression as partial remission (PR) and complete remission (CR) on imaging assessment three months after the completion of treatment.	6 months
Safety(Grade 3-5 AE)	Safety is primarily assessed based on the probability of occurrence of Grade 3-5 adverse effects in different organs according to CTCAE 4.0 (including radiation-related injuries and adverse reactions to immunotherapy).	1-year
Quality of life	The assessment of quality of life is conducted using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Module (EORTC QLQ-H&N 35), which includes eight domains: pain, swallowing, senses, speech, social eating, social contact, sexuality and single items. Each item is scored on a scale from 0 to 100. A high score for a functional scale or global QOL implies a high level of functioning or global QOL, whereas a high score for a symptom scale or single item implies a high level of symptoms.	6 month and 1 year after the treatment

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: December 17, 2023
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: LAHNSCC-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No