Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for HNSCC

Head and Neck Squamous Cell Carcinoma Clinical Trial

— neoCHANCE-2  

Official title:

Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for the Treatment of Resectable Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Trial (neoCHANCE-2 Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05516589
• Other study ID #: ChiECRCT20210621
• Status: Recruiting
• Phase: Phase 2
• Start date: August 20, 2022
• Est. completion date: August 19, 2024

Study information

• Verified date: December 2023
• Source: West China Hospital
• Contact: Xingchen Peng, Professor
• Phone: +8618980606753
• Email: pxx2014[@]scu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To explore the efficiency and safety of TP chemotherapy, tislelizumab, combined with afatinib as a new neoadjuvant treatment regimen for patients with resectable HNSCC.

Description:

More than 60% of patients with Head and neck squamous cell carcinoma (HNSCC) have locally advanced or metastatic disease at the time of diagnosis, with a 5-year overall survival rate of less than 60%. The clinical outcomes of those patients still need to be improved.

Neoadjuvant therapy theoretically could reduce tumor volume, increase organ retention rate, and improve clinical prognosis. However, results from several phase III clinical trials have not proved a significant survival benefit of neoadjuvant chemotherapy for patients with resectable HNSCC except for nasopharyngeal carcinoma. There is an urgent need to explore new neoadjuvant treatment options for those patients.

Immunotherapy such as PD-1/PD-L1 inhibitors have shown excellent efficiency in the treatment of malignancies. Anti-PD-1 therapy is approved as the first-line treatment of recurrent/metastatic HNSCC. Neoadjuvant immunotherapy for the treatment of locally advanced and resectable HNSCC has been demonstrated to be feasible in some trials.

Afatinib, as an irreversible ErbB tyrosine kinase inhibitor (TKI), has been used as the second-line treatment for recurrent and/or metastatic HNSCC. A previous study published in 2018 confirmed that afatinib can be administered safely before surgery.

In summary, we designed this study to explore the efficiency and safety of chemotherapy (TP regimen), anti-PD1 immunotherapy (tislelizumab), combined with EGFR-TKI (afatinib) as a new neoadjuvant treatment regimen for patients with resectable HNSCC, aiming to provide a new treatment option for those patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: August 19, 2024
• Est. primary completion date: August 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years or above.

2. Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following conditions:

• were newly diagnosed and without distant metastasis;

• were deemed surgically resectable evaluated by a head and neck surgeon;

• were willing to undergo surgery.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

4. Adequate organ and bone marrow function:

• absolute neutrophil count = 1.5 × 10^9/L, hemoglobin = 80 g/L, platelets = 80 × 10^9/L;

• ALT, AST and ALP < 2.5× upper limit of normal (ULN), total bilirubin = 2×ULN;

• albumin= 2.8 g/dL;

• creatinine clearance = 60 ml/min;

• INR= 1.5;APTT= 1.5×ULN;

5. Written informed consent.

Exclusion Criteria:

1. History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.)

2. Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.

3. Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.

4. Any of prior therapy with:

• anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs;

• antitumor vaccine;

• any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period;

• major surgery or serious trauma within 4 weeks before the first dose;

• toxicity from prior antitumor therapy has not recovered to = CTCAE Version 5.0 Grade 1 or the level specified by the inclusion/exclusion criteria.

5. With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction < 50%, etc.

6. With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.

7. With hyperthyroidism, or organic thyroid disease.

8. With active infection, or unexplained fever during the screening period or 48 hours before the first dose.

9. With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.

10. History of a clear neurological or psychiatric disorder.

11. History of drug abuse or alcohol abuse.

12. Women who are pregnant or breastfeeding, or have a reproductive plan from the screening period to 3 months after the end of the study, or have sex without contraceptive measures, or are unwilling to take appropriate contraceptive measures.

13. Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.

14. Any other factors that are not suitable for inclusion in this study judged by investigators.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Nab-paclitaxel
260mg/m^2 IV Q3W
• Cisplatin
75mg/m^2 IV Q3W

Biological:
• Tislelizumab
200mg IV Q3W

Drug:
• Afatinib
30mg PO QD

Locations

Country	Name	City	State
China	West China Hospital, Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Pathologic Response	Major pathologic response was defined as fewer than 10% viable tumor cells.	Time of surgery
Secondary	Pathologic Complete Response	Pathologic complete response was defined as the absence of viable tumor cells.	Time of surgery
Secondary	Objective Response Rate	Objective response rate was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria	Up to 8 weeks
Secondary	Adverse Events	Adverse events included adverse events using CTCAE Criteria and unplanned surgery delays.	Up to 12 weeks
Secondary	Disease-free Survival	Disease-free survival was defined as the time from the administration of the first dose to first disease progression or death.	1 year