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

NCT ID: NCT06102395

Last Updated: 2023-10-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2030-04-30

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.

Detailed Description

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 met the inclusion criteria were randomized in a 1:1 ratio and given 2 cycles of pembrolizumab 200 mg d1 + chemotherapy (see the table below for detailed chemotherapy regimens) (experimental group) and 2 cycles of chemotherapy (control group), and were divided according to the patient's condition. layer. If the imaging evaluation is CR after neoadjuvant treatment, radiotherapy (60-70Gy) ± chemotherapy (investigator's choice) will be given as adjuvant treatment; if the imaging evaluation is PR or SD, surgery (within 2 weeks) will be performed, and then standard treatment will be given. treat. If the imaging evaluation is PD, standard treatment will be given. Enrolled patients must closely monitor the adverse reactions of chemotherapy and record the time, grade, treatment measures, outcomes, etc. All patients were reviewed every 3 months for 1 year; after 1 year, they were reviewed every 6 months for 3 years; patient recurrence and survival data were recorded.

The investigators speculate that, compared with the traditional induction chemotherapy regimen, the induction chemotherapy regimen of pembrolizumab combined with chemotherapy may be safer and more effective, and easier for clinical application. At present, there are no research reports on the induction chemotherapy of pembrolizumab combined with cisplatin and nab-paclitaxel for patients with locally advanced operable head and neck squamous cell carcinoma. We intend to conduct a randomized controlled study on the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in Chinese patients with operable head and neck squamous cell carcinoma, and provide a basis for the neoadjuvant therapy of pembrolizumab combined with chemotherapy.

Conditions

Head and Neck Squamous Cell Carcinoma; Neoadjuvant Therapy; Pembrolizumab

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab combined with standard chemotherapy

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Nedaplatin

Intervention Type: DRUG

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

Nab paclitaxel

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Liposomal paclitaxel

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: DRUG

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

Standard chemotherapy

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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Nedaplatin

Intervention Type: DRUG

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

Nab paclitaxel

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Liposomal paclitaxel

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: DRUG

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

Interventions

Pembrolizumab

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Nedaplatin

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

Intervention Type: DRUG

Nab paclitaxel

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Liposomal paclitaxel

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

Intervention Type: DRUG

Fluorouracil

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with stage IIIA-IVB head and neck squamous cell carcinoma confirmed by histology and/or cytology;

2. Have not received immunotherapy in the past;

3. The researchers believe that he can safely receive pembrolizumab combined with chemotherapy or neoadjuvant chemotherapy;

4. Age ≥18 years;

5. ECOG 0-2;

6. Measurable disease as defined by RECIST v1.1;

7. Organs function normally;

8. 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;

9. Male participants must not donate sperm throughout the study and for 180 days after the last study treatment.

Exclusion Criteria

1. Presence of distant metastasis;

2. 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);

3. received a live vaccine within 30 days before enrollment;

4. Diagnosed with immunodeficiency or receiving systemic steroid treatment or any other form of immunosuppressive treatment within 7 days before enrollment;

5. Have imaging detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or cancerous meningitis;

6. Have undergone surgery before commencing the study or have failed to recover adequately from toxicity or complications resulting from the intervention;

7. Previous allogeneic tissue/solid organ transplant;

8. Severe hypersensitivity reaction (≥Grade 3) to pembrolizumab or any of its excipients, radiotherapy, platinum, paclitaxel, 5-FU or their analogs;

9. Have an active autoimmune disease requiring systemic therapy in the past 2 years;

10. History of (non-infectious) pneumonia requiring steroid treatment;

11. Have a history of human immunodeficiency virus (HIV) infection;

12. 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).

13. 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.);

14. Have a known history of mental illness or substance abuse disorder

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tongren Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhigang Huang

Role: STUDY_CHAIR

Beijing Tongren Hospital

Locations

Beijing Tongren Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhigang Huang

Role: CONTACT

huangzhigang1963@sohu.com

+86 13701208337

Yang Zhang

Role: CONTACT

Zhangyangent@163.com

+86 13311365369

Facility Contacts

Yang Zhang

Role: primary

zhangyazhangyangent@163.comngent@163.com

+86 13311365369

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCT23456

Identifier Type: -

Identifier Source: org_study_id