Comparing Neoadjuvant Chemotherapy Combined With PD-1 Inhibitor Versus Neoadjuvant Chemotherapy in Locally Advanced Laryngeal and Hypopharyngeal Carcinoma

NCT06957938 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: PRECEDE2504318-4
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemotherapy combined with immunotherapy has achieved promising pathological remission rates in locally advanced head and neck squamous cell carcinoma and has offered new hope for patients with locally advanced laryngeal and hypopharyngeal cancer. In our center's previous phase II study on locally advanced laryngeal and hypopharyngeal cancer, neoadjuvant chemotherapy combined with immunotherapy showed good 1 - year laryngeal preservation rate and 1 - year PFS rate. However, in locally advanced laryngeal and hypopharyngeal cancer, whether neoadjuvant chemotherapy combined with PD-1 inhibitor, compared with neoadjuvant chemotherapy, can improve laryngeal preservation survival, event - free survival and overall survival remains unclear. Thus, this study aims to explore in locally advanced laryngeal and hypopharyngeal cancer whether neoadjuvant immuno - chemotherapy, compared with neoadjuvant chemotherapy, can improve laryngeal preservation survival and bring benefits in quality of life.

Conditions

Laryngeal Carcinoma; Hypopharyngeal Carcinoma

Keywords

Neoadjuvant chemotherapy; Induction chemotherapy; Immunotherapy; anti-PD-1 antibody; PD-1 inhibitor; Tislelizumab; surgery; radiation; Locally advanced disease; Laryngeal preservation; Laryngeal cancer; Hypopharyngeal cancer; Head and neck cancer; Head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• 2-year Laryngectomy-free Survival Rate

  Laryngectomy-free survival (LFS) is defined as the time from randomization to the first occurrence of local recurrence, total laryngectomy, or death, with the time calculated based on the first event that occurs.

  2 year

Secondary Outcomes (9)

• Early response rate

  day 14 to day 21

• Objective response rate to neoadjuvant therapy

  day 56 to day 63

• 2-year Event-free Survival Rate

  2 year

• 2-year Overall Survival Rate

  2 year

• 2-year Laryngectomy-free Survival Rate with a functional larynx

  2 year

Study Arms (2)

Neoadjuvant chemotherapy combined with Tislelizumab

EXPERIMENTAL

Neoadjuvant chemotherapy combined with Tislelizumab, followed by chemo-radiation or surgery and adjuvant (chemo-)radiation, then maintenance therapy of Tislelizumab.

Drug: Neoadjuvant Chemotherapy (NACT); Drug: Neoadjuvant and maintenance Tislelizumab; Radiation: Concurrent chemo-radiotherapy (CCRT); Procedure: Surgery and adjuvant (chemo-)radiotherapy

Neoadjuvant chemotherapy

ACTIVE COMPARATOR

Neoadjuvant chemotherapy, followed by chemo-radiation or surgery and adjuvant (chemo-)radiation.

Drug: Neoadjuvant Chemotherapy (NACT); Radiation: Concurrent chemo-radiotherapy (CCRT); Procedure: Surgery and adjuvant (chemo-)radiotherapy

Interventions

Neoadjuvant Chemotherapy (NACT) DRUG

Neoadjuvant Chemotherapy with paclitaxel (or albumin - bound paclitaxel) and cisplatin

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy combined with Tislelizumab

Neoadjuvant and maintenance Tislelizumab DRUG

Neoadjuvant and maintenance Tislelizumab

Neoadjuvant chemotherapy combined with Tislelizumab

Concurrent chemo-radiotherapy (CCRT) RADIATION

Concurrent chemo-radiotherapy (CCRT), with cisplatin-based chemotherapy

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy combined with Tislelizumab

Surgery and adjuvant (chemo-)radiotherapy PROCEDURE

Definitive surgery, with adjuvant (chemo-)radiotherapy, depending on pathologic findings.

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy combined with Tislelizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have signed the informed consent form and are willing to complete the study according to the protocol.
• Age ≥18 years and ≤75 years.
• Histologically confirmed squamous cell carcinoma of the larynx or hypopharynx.
• Locally advanced laryngeal or hypopharyngeal cancer that requires total laryngectomy and is amenable to total laryngectomy according to surgical assessment.
• At least one measurable lesion before treatment, which meets the criteria for "measurable lesion" according to RECIST 1.1 criteria.
• An expected survival of \>3 months.
• ECOG performance status of 0-1.
• Adequate organ function, meeting the following requirements:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
• Platelet count ≥100×10\^9/L;
• Hemoglobin ≥9 g/dL;
• Serum albumin ≥2.8 g/dL;
• Total bilirubin ≤1.5×ULN, ALT, AST, and/or ALP ≤3×ULN;
• Serum creatinine ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault, see Appendix III);
• Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN (patients on stable doses of anticoagulant therapy, such as low-molecular-weight heparin or warfarin, with INR within the therapeutic range of the anticoagulant, are eligible).

You may not qualify if:

• Patients who have been confirmed to have distant metastasis on imaging assessment before treatment.
• Patients who have previously received immune checkpoint inhibitor therapy.
• Patients who have previously received radiotherapy to the head and neck region.
• Patients who have had or currently have other malignancies (except for malignancies that have been cured and have been cancer-free for more than 5 years, such as basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid cancer); if a patient has both hypopharyngeal cancer and esophageal cancer, and the esophageal lesion and hypopharyngeal lesion are anatomically non-adjacent, they should be diagnosed with multiple primary tumors and will not be eligible for enrollment.
• Uncontrolled cardiac symptoms or diseases, such as: a. NYHA Class II or higher heart failure; b. unstable angina; c. myocardial infarction within the past year; d. clinically significant supraventricular or ventricular arrhythmias that are not well controlled with medication.
• Patients who have received any of the following treatments:
• Received any investigational drug within 4 weeks before the first dose of the study drug.
• Enrolled in another clinical study concurrently, unless it is an observational (non-interventional) clinical study.
• Require systemic treatment with corticosteroids (more than 10 mg prednisone equivalent per day) or other immunosuppressive agents within 2 weeks before the first dose of the study drug, except for corticosteroids used for local inflammation and prevention of allergies and nausea/vomiting. Other special circumstances should be discussed with the investigator. In the absence of active autoimmune disease, the use of inhaled or topical steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day prednisone equivalent is permitted.
• Received anti-tumor vaccines or live vaccines within 4 weeks before the first dose of the study drug (if the patient has received a COVID-19 vaccine, the interval between vaccination and treatment should be more than 2 weeks).
• Underwent major surgery or had a severe injury within 4 weeks before the first dose of the study drug.
• Patients who have had a severe infection (CTCAE \> Grade 2) within 4 weeks before the first dose of the study drug, such as severe pneumonia, bacteremia, or infectious complications requiring hospitalization; baseline chest imaging showing active pulmonary inflammation; symptoms and signs of infection within 4 weeks before the first dose of the study drug or requiring oral or intravenous antibiotic treatment.
• Patients with active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); however, this does not include autoimmune hypothyroidism treated with a stable dose of thyroid hormone replacement therapy; type 1 diabetes treated with a stable dose of insulin; vitiligo or childhood asthma/allergies that have healed and do not require any intervention in adulthood.
• Patients with a history of immunodeficiency, including positive HIV test results, or those with other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation.
• Patients with a history of interstitial lung disease (excluding radiation pneumonitis that has not been treated with corticosteroids) or non-infectious pneumonia.

Sponsors & Collaborators

• Fudan University: lead
• Sun Yat-sen University Cancer Center (SUSUCC): collaborator
• Fujian Cancer Hospital: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (2)

• Fang Q, Xu P, Cao F, Wu D, Liu X. PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study. Cancer Immunol Immunother. 2023 Dec;72(12):4161-4168. doi: 10.1007/s00262-023-03550-z. Epub 2023 Oct 7.

  PMID: 37804437 BACKGROUND

• Ou X, Zhai R, Wei W, Chen J, Ou D, Liao T, Xu T, Zhu Y, Wang Y, Huang S, Shi R, Wu B, Chen T, Li Y, Yang Z, Zhou C, Liu Y, Jiang Z, Zeng M, Liu X, Ji D, Ying H, Zhang Z, Hu C, Lu X, Ji Q, He X, Wang Y. Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial. Clin Cancer Res. 2024 Jan 17;30(2):344-355. doi: 10.1158/1078-0432.CCR-23-2398.

  PMID: 37955629 BACKGROUND

MeSH Terms

Conditions

Laryngeal Neoplasms; Hypopharyngeal Neoplasms; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Neoadjuvant Therapy; Surgical Procedures, Operative; Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Yu Wang, M.D., professor, Chief

  Department of head and neck surgery, Fudan University Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Wang, M.D., professor

CONTACT

+86-18017312437; neck130@hotmail.com

Xiaomin Ou, M.D.

CONTACT

+86-18017317872; xiaomin_ou@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Professor

Study Record Dates

• First Submitted: April 27, 2025
• First Posted: May 6, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2031
• Last Updated: May 8, 2025

Record last verified: 2025-04

Locations

CN (1)