Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

Safety and Efficacy of Pembrolizumab in Combination With Low-dose PF (Cisplatin and 5-Fluorouracil) as Neoadjuvant Treatment for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Multi-center, Single-arm Clinical Study Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05446467
• Other study ID #: KPF20220630
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2022
• Est. completion date: March 1, 2026

Study information

• Verified date: March 2024
• Source: Zhejiang Provincial People's Hospital
• Contact: Jiajie Xu, PhD
• Phone: +86 13600517252
• Email: 03kqyxxjj[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase Ⅱ open label multi-cencter clinical trail to evaluate the efficacy and safety of pembrolizumab combined with low-dose PF (cisplatin + 5-fluorouracil) in the neoadjuvant treatment of locally advanced head and neck squamous cell carcinoma

Description:

The investigatorsdesigned a multi-center, single-arm, small sample clinical pilot study. In the clinical trial, patients were given regimes of induction therapy with PLPF (Pembrolizumab + Low dose- P (Platinum) F (5-Fluorouracil)): 6 cycles of Pembrolizumab treatment. Herein, the investigators describe eight consecutive unselected LA SCCHN (Locally Advanced Head and Neck Squamous Cell Carcinoma) patients based on 6 completed cycles of PLPF induction therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 1, 2026
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age = 18 years old, = 85 years old

2. Histologically or cytologically proven squamous cell carcinoma of the head and neck; Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx

3. Measurable primary lesions per RECIST 1.1 criteria

4. Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions)

5. ECOG performance status of 0 or 1

6. Selective standard surgery+ standard adjuvant chemo-radiotherapy/radiotherapy as judged by the investigator

7. No active autoimmune disease

8. No concurrent malignancy

9. Life expectancy is estimated to be over 3 months

10. Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO)

11. No abvious signs of hematological disorders, ANC=1.5×109 /L, platelets =100×109 /L, Hb= 90 g/L,WBC =3.0×109 /L before enrollment, no blood transfusion and bleeding tendency within 7 days

12. ALT,AST and ALP = 2.5 × upper limit of normal (ULN); Serum bilirubin = 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin = 3 x ULN

13. Serum creatinine =1.5 or creatinine clearance>50 mL/min

14. HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays

15. Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent

Exclusion Criteria:

1. Multiple organs failure

2. HPV p16 positive oropharyngeal cancer

3. Patients with local advanced head and neck squamous cell carcinoma stage T4B and/or N3

4. Patients with distant metastasis

5. Uncontrolled serious diseases that, as assessed by investigator, may affect the subject's treatment with the study protocol, such as serious heart disease, cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc.

6. Diagnosis of dementia, altered mental status or any mental illness that would prevent subjects understanding or giving informed consent or completing questionnaires

7. Subjects with = Grade 2 peripheral neuropathy according to CTCAE V5.0

8. Subjects with = Grade 2 hearing impairment according to CTCAE V5.0

9. History of allergy or hypersensitivity to any of the therapeutic ingredients

10. Diagnosis of malignancy within 5 years prior to screening, including HNSCC (other than current HNSCC) and other malignancies; Eligibility is achieved if all of the following criteria are met: malignancies received curative therapy, such as adequately treated cervical carcinoma in situ, non-melanoma cutaneum carcinoma, localized prostate cancer after radical operation, breast ductal carcinoma in situ after radical operation; There was also no evidence of recurrence or metastasis based on imaging and tumor markers

11. Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)

12. Patients diagnosed with nasopharyngeal carcinoma or squamous cell carcinoma whose lesions are located in parts other than the oral cavity, oropharynx, larynx and hypopharynx (such as sinuses, paranasal sinuses and unknown primary site)

13. Participated in other clinical intervention trials or received other investigational therapies within 30 days prior to screening

14. Patients received systemic corticosteroids (prednisone equivalent dose>10mg/day) or other immunosuppressive drugs within 14 days prior to randomization. If there is no active autoimmune disease, inhaled or topical steroid hormones and adrenal hormone replacement therapy with prednisone equivalent doses>10mg per day are permitted

15. Pregnant or breastfeeding; Subjects of childbearing age refuse to accept contraceptive measures

16. Patients unfit for study as assessed by the investigator

17. Received systemic antibiotics within 1 weeks prior to first dose of study therapy or active infection requiring treatment

18. Known history of HBV infection (defined as HBsAg positive) or active HCV infection (defined as HCV RNA detected)

19. Has received live vaccine during study or within 30 days prior to first dose of study therapy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Combination Product:
• pembrolizumab+cisplatin + 5-FU
ivgtt, pembrolizumab 200mg d1+cisplatin20 mg/m2 qd d1-d3 + 5-fluorouracil 3000mg/m2 last for 120hours, six circles. Subjects will undergo surgery after receiving neoadjuvant chemotherapy within 3 weeks, followed by adjuvant therapy and pembrolizumab alone maintenance treatment.

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital School of Medicine,Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Ningbo Medical Center Lihuili Hospital	Ningbo
China	Tianjin Cancer Hospital Airport Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Outcome2	Pembrolizumab in combination with low-dose PF (cisplatin + 5-fluorouracil) stratified by CPS PD-L1 status (CPS PD-L1<1, CPS PD-L1>1, and CPS PD-L1 not evaluable/uncertain) ) for the primary CR rate of stage 1 neoadjuvant therapy for locally advanced HNSCC	Up to 6 months
Other	Exploratory Outcome:biomarkers and single-cell sequencing	Immune cell flow analysis, blood MRD detection analysis, single-cell sequencing analysis before and after immune neoadjuvant therapy.	up to 2 years
Primary	Primary site CR rate after neoadjuvant therapy	Measure the primary site CR rate after neoadjuvant therapy	Up to 6 months
Secondary	Incidence of adverse reactions during neoadjuvant therapy	Incidence of adverse reactions during neoadjuvant therapy	up to 2 years
Secondary	The stages of descent after neoadjuvant therapy	The stage of the tumor after neoadjuvant therapy according to the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition) will be evaluated by treating physicians.	up to 6 months
Secondary	Primary site pCR rate after neoadjuvant therapy	Primary site pCR rate after neoadjuvant therapy	Up to 6 months
Secondary	EFS	EFS is defined as the time from the initial treatment date to the first documented event date, including disease progression, local or distant metastasis as assessed by image or biopsy, or death from any cause, whichever comes first.	up to 2 years
Secondary	DFS	DFS is defined as the time from surgery to disease progression or death due to any cause, whichever comes first.	up to 2 years
Secondary	PFS	PFS is defined as the time from initial treatment to disease progression or death from any cause, whichever comes first.	up to 2 years
Secondary	OS	OS is defined as the time from initial treatment to death due to any cause.	2 years
Secondary	One year local control rate	One year local control rate	up to 6 months
Secondary	1-, 2-year survival rates	1-, 2-year survival rates	up to 2 years