Intra-arterial Chemotherapy Combined with Radiotherapy and Immunotherapy for HNSCC

A Prospective, Single-center, Open-label Phase II Clinical Study of Intra-arterial Chemotherapy Combined with Concurrent Radiotherapy and Tislelizumab-jsgr in the Treatment of T4bNanyM0 HNSCC

This study pioneers a novel approach by integrating a new auxiliary chemo-immunotherapy regimen, which is then followed by an evaluation of the potential for surgical resection. For those patients who remain non-resectable, a tailored treatment plan is proposed, consisting of arterial infusion chemotherapy in conjunction with radiotherapy, succeeded by a series of immune checkpoint inhibitors. The efficacy and safety of this integrated therapeutic strategy are meticulously assessed, with the goal of enhancing survival outcomes for patients with T4bNanyM0 HNSCC.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Tislelizumab-jsgr; Drug: Cisplatin; Drug: Albumin-Bound Paclitaxel; Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaohong Chen, Dr.; Phone Number: +86-10-58266699; Email: trchxh@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 10000
      • Recruiting
      • Beijing Tongren Hospital Affiliated to Capital Medical University
      • Contact: Xiaohong Chen, Dr.; Phone Number: +86-10-58266699

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with T4bNanyM0 Head and neck squamous cell carcinoma (hypopharyngeal cancer, laryngeal cancer, oropharyngeal cancer or oral cavity) with a confirmed diagnosis by histology and/or cytology;
• Expected survival ≥3 months, with adequate organ function;
• Investigators believe they can safely receive treatment with PD-1 combined with platinum and albumin-bound paclitaxel;
• Age ≥18 years;
• ECOG score of 0-1;
• Measurable disease as defined by RECIST v1.1;
• Adequate bone marrow reserve and organ function: Absolute neutrophil count (ANC) ≥1,000/microliter (mcL), platelets ≥75,000/mcL, hemoglobin ≥8g/dL, without transfusion or dependence on erythropoietin (EPO) (within 7 days after assessment);
• Renal function: Serum creatinine ≤1.5 times the upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥60mL/min with creatinine levels > 1.5 times the institutional ULN. (GFR can also be used in place of creatinine or CrCl). Creatinine clearance should be calculated according to institutional standards;
• Liver function: For subjects with a total bilirubin level >1.5 ULN, serum total bilirubin ≤1.5 times ULN or direct bilirubin ≤ULN; For patients with liver metastases, aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5 times ULN OR ≤5 times ULN; Albumin > 2.5 mg/dL;
• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN, if the subject is receiving anticoagulant therapy, PT or PTT should be within the permissible range of the anticoagulant used;
• Females should agree to use contraceptive measures (such as intrauterine device (IUD), oral contraceptives, or condoms) during the study and for 6 months after the study ends; Negative serum or urine pregnancy test within 7 days before study entry, and must be non-lactating patients; Males should agree to use contraceptive measures during the study and for 6 months after the study ends.

Exclusion Criteria:

• Patients with a history of prior immunotherapy, radiotherapy, and treatment with EGFR monoclonal antibodies;
• Patients with a history of other (including unknown primary) malignant tumors within the past 5 years;
• Patients who are intolerant to radiotherapy post-surgery;
• Patients known to be allergic to the study medication or its active ingredients, excipients;
• Patients with any unstable systemic diseases, including but not limited to: severe infections, uncontrolled diabetes, unstable angina, cerebrovascular accidents or transient ischemic attacks, myocardial infarction, congestive heart failure, serious arrhythmias requiring medication, liver, kidney, or metabolic disorders;
• Patients with potential immune deficiencies, chronic infections, including HIV, hepatitis, tuberculosis (TB), or autoimmune diseases;
• Patients with potential hematological issues, including bleeding disorders, known prior gastrointestinal bleeding requiring intervention within the past 6 months, active pulmonary embolism or deep vein thrombosis (DVT) that is unstable on anticoagulation regimens;
• A history or any evidence of active noninfectious pneumonia;
• Known active central nervous system (CNS) metastases and/or leptomeningeal disease or carcinomatous meningitis. Subjects with previously treated brain metastases may participate if they are stable (no evidence of imaging progression for at least four weeks prior to the first trial treatment and any neurological symptoms have returned to baseline), with no new or enlarging evidence of brain metastases, and are not on steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability;
• Concurrent use (or receipt) of medications within 7 days prior to Day 1 of Cycle 1 that may affect drug metabolism;
• Pregnant or breastfeeding, or expecting to become pregnant or father a child during the anticipated trial period;
• Any uncontrollable concomitant diseases, including but not limited to persistent or active infections, symptomatic congestive heart failure, unstable angina, arrhythmias;
• Prolonged corrected QT (QTc) interval > 475 ms on screening EKG;
• Ejection fraction <40% on 2D echocardiogram (ECHO) at screening;
• Any serious medical or psychiatric illness/condition, including substance use disorders, that may interfere with or limit adherence to study requirements/treatment in the investigator's judgment;
• Active autoimmune disease requiring systemic treatment in the past 2 years (i.e., the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapies (e.g., thyroid hormone, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency, etc.) are not considered a form of systemic treatment.

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: RT + IAC + Anti-PD-1 antibody; Patients must undergo Multi-Disciplinary Treatment evaluation after receiving 3 cycles of neoadjuvant therapy (Tislelizumab-jsgr combined with platinum-based chemotherapy). For operable patients, Radical surgery followed by adjuvant standard (chemo)radiotherapy plus Tislelizumab-jsgr (Q3W 17 cycles). For inoperable patients, Intra-arterial Chemotherapy concurrent with Radical radiotherapy followed by Tislelizumab-jsgr (Q3W 17 cycles).

Drug: Tislelizumab-jsgr; 200mg, Q3W; Drug: Cisplatin; 60-75 mg/㎡, Q3W; Drug: Albumin-Bound Paclitaxel; 260 mg/㎡, Q3W; Radiation: Radiotherapy; Radical Radiotherapy or adjuvant Radiotherapy per guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year Event-free Survival rate (1y-EFS rate)	EFS is the time from the starting date of neoadjuvant therapy to the date of first record of any of the following events: radiographic disease progression; local or distant progression or recurrence as assessed with imaging or biopsy as indicated; or death due to any cause. Radiographic disease progression during neoadjuvant phase that precludes surgery will be considered an event; a secondary malignancy will not be considered an event.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	Up to 30 days post-neoadjuvant
Pathological Complete Response (pCR)	Pathological complete response (pCR) is measured as the percentage of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.	Up to 30 days post-surgery
Major Pathological Response (MPR)	The percentage of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.	Up to 30 days post-surgery
Overall Survival (OS)	OS was defined as the time from starting date of neoadjuvant therapy to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.	Up to 5 years
Percentage of Participants Experiencing An Adverse Event (AEs)	Percentage of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy	through study completion, an average of 2 years
Local Recurrence-free Survival (LRFS)	Percentage of patients in a treatment group who are alive without local recurrence.	through study completion, an average of 5 years
Distant Metastases-free Survival (DMFS)	DMFS will be defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first.	through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: December 8, 2024
• First Posted (Estimated): December 10, 2024

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Tislelizumab; Paclitaxel
• Other Study ID Numbers: TREC2023-KY073

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
• product manufactured in and exported from the U.S.: No