Clinical trial NCT05446467: Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: Zhejiang Provincial People's Hospital
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary site CR rate after neoadjuvant therapy
timeFrame: Up to 6 months
Secondary outcomes:
measure: Incidence of adverse reactions during neoadjuvant therapy
timeFrame: up to 2 years
measure: The stages of descent after neoadjuvant therapy
timeFrame: up to 6 months
measure: Primary site pCR rate after neoadjuvant therapy
timeFrame: Up to 6 months
measure: EFS
timeFrame: up to 2 years
measure: DFS
timeFrame: up to 2 years
measure: PFS
timeFrame: up to 2 years
measure: OS
timeFrame: 2 years
measure: One year local control rate
timeFrame: up to 6 months
measure: 1-, 2-year survival rates
timeFrame: up to 2 years
Other outcomes:
measure: Exploratory Outcome2
timeFrame: Up to 6 months
measure: Exploratory Outcome：biomarkers and single-cell sequencing
timeFrame: up to 2 years
Locations:
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital School of Medicine,Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital Airport Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
Study officials:
affiliation: Zhejiang Provincial People's Hospital
name: Minghua Ge, PhD
role: PRINCIPAL_INVESTIGATOR
References: