Evaluating the Efficacy and Safety of Pembrolizumab Plus Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC

NCT06102395 | Recruiting Phase 3

• 1 other identifier: NCT23456
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, open-label, multi-center phase III study; patients with untreated stage IIIA to stage IVB head and neck squamous cell carcinoma (including oral cavity cancer, oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer) who meet the inclusion criteria are randomized 1:1 and given pembrolizumab 200 mg d1+ chemotherapy for 2 cycles (experimental group), 2 cycles of chemotherapy (control group), and then stratified according to the patient's condition. If the imaging evaluation after neoadjuvant treatment is (complete response, CR), adjuvant radiotherapy will be given; if the imaging evaluation is (partial response, PR) or (stable disease, SD), surgery (within 2 weeks) will be performed, followed by standard treatment. The main research hypothesis of this study: pembrolizumab combined with standard chemotherapy can significantly improve the rate of pathological complete response (pCR) compared with standard chemotherapy.

Conditions

Head and Neck Squamous Cell Carcinoma; Neoadjuvant Therapy; Pembrolizumab

Outcome Measures

Primary Outcomes (2)

• Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy neoadjuvant therapy in patients with locally advanced head and neck squamous cell carcinoma

  pCR was defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy

  12 week

• Pathological complete response rate (pCR) of standard chemotherapy neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma

  pCR was defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy

  12 week

Secondary Outcomes (18)

• The objective response rate (ORR) of neoadjuvant therapy with pembrolizumab combined with standard chemotherapy

  12 week

• The objective response rate (ORR) of neoadjuvant chemotherapy with standard chemotherapy

  6 week

• The 1-year and 2-year event-free survival rates (1y-EFS, 2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy

  2 year

• The 1-year and 2-year event-free survival rate (1y-EFS, 2y-EFS) after neoadjuvant chemotherapy with standard chemotherapy

  2 year

• The functional preservation rate of pembrolizumab combined with standard chemotherapy

  3 year

Study Arms (2)

Pembrolizumab combined with standard chemotherapy

EXPERIMENTAL

Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m\^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m\^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m\^2, IV, day 1 of Q3W or docetaxel 75 mg/m\^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m\^2, IV, day 1 of Q3W or fluorouracil 750 mg/m\^2, IV, day 1-5 of Q3W）; total 2 cycle

Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Nedaplatin; Drug: Nab paclitaxel; Drug: Docetaxel; Drug: Liposomal paclitaxel; Drug: Fluorouracil

Standard chemotherapy

ACTIVE COMPARATOR

Patients receive platinum (cisplatin 75 mg/m\^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m\^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m\^2, IV, day 1 of Q3W or docetaxel 75 mg/m\^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m\^2, IV, day 1 of Q3W or fluorouracil 750 mg/m\^2, IV, day 1-5 of Q3W）; total 2 cycle

Drug: Cisplatin; Drug: Carboplatin; Drug: Nedaplatin; Drug: Nab paclitaxel; Drug: Docetaxel; Drug: Liposomal paclitaxel; Drug: Fluorouracil

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg, IV, on day1 of Q3W, 2 cycle

Pembrolizumab combined with standard chemotherapy

Cisplatin DRUG

Cisplatin 75 mg/m\^2, IV, day 1 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Carboplatin DRUG

Carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Nedaplatin DRUG

Nedaplatin 80-100 mg/m\^2, IV, day 2-4 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Nab paclitaxel DRUG

Nab paclitaxel 260 mg/m\^2, IV, day 1 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Docetaxel DRUG

Docetaxel 75 mg/m\^2, IV, day 1 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Liposomal paclitaxel DRUG

Liposomal paclitaxel 135-175 mg/m\^2, IV, day 1 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Fluorouracil DRUG

Fluorouracil 750 mg/m\^2, IV, day 1-5 of Q3W

Pembrolizumab combined with standard chemotherapy; Standard chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients with stage IIIA-IVB head and neck squamous cell carcinoma confirmed by histology and/or cytology;
• Have not received immunotherapy in the past;
• The researchers believe that he can safely receive pembrolizumab combined with chemotherapy or neoadjuvant chemotherapy;
• Age ≥18 years;
• ECOG 0-2;
• Measurable disease as defined by RECIST v1.1;
• Organs function normally;
• Female and male participants of reproductive potential must agree to use appropriate contraception throughout the study period and for 180 days after the last study treatment;
• Male participants must not donate sperm throughout the study and for 180 days after the last study treatment.

You may not qualify if:

• Presence of distant metastasis;
• Female subjects with a positive urine pregnancy test within 72 hours before the start of the study or within 24 hours after starting radiation therapy (with or without cisplatin);
• received a live vaccine within 30 days before enrollment;
• Diagnosed with immunodeficiency or receiving systemic steroid treatment or any other form of immunosuppressive treatment within 7 days before enrollment;
• Have imaging detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or cancerous meningitis;
• Have undergone surgery before commencing the study or have failed to recover adequately from toxicity or complications resulting from the intervention;
• Previous allogeneic tissue/solid organ transplant;
• Severe hypersensitivity reaction (≥Grade 3) to pembrolizumab or any of its excipients, radiotherapy, platinum, paclitaxel, 5-FU or their analogs;
• Have an active autoimmune disease requiring systemic therapy in the past 2 years;
• History of (non-infectious) pneumonia requiring steroid treatment;
• Have a history of human immunodeficiency virus (HIV) infection;
• Have a history of hepatitis B or be positive for hepatitis B virus (defined as a positive reaction to hepatitis B surface antigen \[HBsAg\]) or active hepatitis C (defined as detection of hepatitis C virus \[HCV\] ribonucleic acid).
• Have any medical history, treatment, or laboratory abnormalities that could confound the study results, interfere with participant participation throughout the study, or be detrimental to the best interests of the participant (e.g., Hashimoto's thyroiditis, etc.);
• Have a known history of mental illness or substance abuse disorder

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Cisplatin; Carboplatin; nedaplatin; Taxes; Docetaxel; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zhigang Huang

  Beijing Tongren Hospital

  STUDY CHAIR

Central Study Contacts

Zhigang Huang

CONTACT

+86 13701208337; huangzhigang1963@sohu.com

Yang Zhang

CONTACT

+86 13311365369; Zhangyangent@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: October 26, 2023
• Study Start: May 1, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2030
• Last Updated: October 30, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)