Clinical trial NCT06102395: Evaluating the Efficacy and Safety of Pembrolizumab Plus Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC
Official title: EFFECT-neo: A Prospective, Open-label, Multicenter Phase III Study to Evaluate Efficacy and Safety of Pembrolizumab Combined With Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Neoadjuvant Therapy
Pembrolizumab
Lead sponsor: Beijing Tongren Hospital
Sponsor class: OTHER
First posted: 2023-10-26
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy neoadjuvant therapy in patients with locally advanced head and neck squamous cell carcinoma
timeFrame: 12 week
measure: Pathological complete response rate (pCR) of standard chemotherapy neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma
timeFrame: 12 week
Secondary outcomes:
measure: The objective response rate (ORR) of neoadjuvant therapy with pembrolizumab combined with standard chemotherapy
timeFrame: 12 week
measure: The objective response rate (ORR) of neoadjuvant chemotherapy with standard chemotherapy
timeFrame: 6 week
measure: The 1-year and 2-year event-free survival rates (1y-EFS, 2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy
timeFrame: 2 year
measure: The 1-year and 2-year event-free survival rate (1y-EFS, 2y-EFS) after neoadjuvant chemotherapy with standard chemotherapy
timeFrame: 2 year
measure: The functional preservation rate of pembrolizumab combined with standard chemotherapy
timeFrame: 3 year
measure: The functional preservation rate of standard chemotherapy
timeFrame: 3 year
measure: The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy
timeFrame: 2 year
measure: The 2-year overall survival rate (2y-OS) after Neoadjuvant Therapy with standard chemotherapy
timeFrame: 2 year
measure: Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy as neoadjuvant therapy in patients of locally advanced head and neck squamous cell carcinoma with CPS (combined positive score) ≥1
timeFrame: 12 week
measure: Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy as neoadjuvant therapy in patients of locally advanced head and neck squamous cell carcinoma with CPS (combined positive score) <1
timeFrame: 12 week
measure: The 2-year event-free survival rates (2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy with CPS (combined positive score) ≥1
timeFrame: 2 year
measure: The 2-year event-free survival rates (2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy with CPS (combined positive score) <1
timeFrame: 2 year
measure: The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy with CPS(combined positive score) ≥1
timeFrame: 2 year
measure: The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy with CPS(combined positive score) <1
timeFrame: 2 year
measure: Incidence of Treatment-Emergent Adverse Events (TRAEs) of pembrolizumab combined with standard chemotherapy in neoadjuvant therapy
timeFrame: 3 year
measure: Incidence of Treatment-Emergent Adverse Events (TRAEs) of neoadjuvant chemotherapy with standard chemotherapy
timeFrame: 3 year
measure: The quality of life of pembrolizumab combined with standard chemotherapy neoadjuvant therapy measured by KPS (Karnofsky performance status) scores
timeFrame: 3 year
measure: The quality of life of standard chemotherapy neoadjuvant therapy measured by KPS (Karnofsky performance status) scores
timeFrame: 3 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital
state: Beijing
Study officials:
affiliation: Beijing Tongren Hospital
name: Zhigang Huang
role: STUDY_CHAIR
References: