Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for HNSCC (neoCHANCE-2)
Primary Purpose
Head and Neck Squamous Cell Carcinoma
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nab-paclitaxel
Cisplatin
Tislelizumab
Afatinib
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring Head and Neck Cancer, Neoadjuvant therapy, Immunotherapy, EGFR-TKI, Chemotherapy
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or above.
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.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
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;
- Written informed consent.
Exclusion Criteria:
- 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.)
- Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
- Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
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.
- 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.
- With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
- With hyperthyroidism, or organic thyroid disease.
- With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
- With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
- History of a clear neurological or psychiatric disorder.
- History of drug abuse or alcohol abuse.
- 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.
- Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.
- Any other factors that are not suitable for inclusion in this study judged by investigators.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Cohort
Arm Description
Participants will receive TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on days 1-3); Tislelizumab 200mg IV every 3 weeks x 2 cycles; Afatinib 30mg PO everyday x 6 weeks.
Outcomes
Primary Outcome Measures
Major Pathologic Response
Major pathologic response was defined as fewer than 10% viable tumor cells.
Secondary Outcome Measures
Pathologic Complete Response
Pathologic complete response was defined as the absence of viable tumor cells.
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
Adverse Events
Adverse events included adverse events using CTCAE Criteria and unplanned surgery delays.
Disease-free Survival
Disease-free survival was defined as the time from the administration of the first dose to first disease progression or death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05516589
Brief Title
Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for HNSCC
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 20, 2022 (Anticipated)
Primary Completion Date
August 19, 2023 (Anticipated)
Study Completion Date
August 19, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma
Keywords
Head and Neck Cancer, Neoadjuvant therapy, Immunotherapy, EGFR-TKI, Chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Cohort
Arm Type
Experimental
Arm Description
Participants will receive
TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on days 1-3);
Tislelizumab 200mg IV every 3 weeks x 2 cycles;
Afatinib 30mg PO everyday x 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Albumin-bound paclitaxel, Abraxane
Intervention Description
260mg/m^2 IV Q3W
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
CDDP
Intervention Description
75mg/m^2 IV Q3W
Intervention Type
Biological
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
BGB-A317
Intervention Description
200mg IV Q3W
Intervention Type
Drug
Intervention Name(s)
Afatinib
Intervention Description
30mg PO QD
Primary Outcome Measure Information:
Title
Major Pathologic Response
Description
Major pathologic response was defined as fewer than 10% viable tumor cells.
Time Frame
Time of surgery
Secondary Outcome Measure Information:
Title
Pathologic Complete Response
Description
Pathologic complete response was defined as the absence of viable tumor cells.
Time Frame
Time of surgery
Title
Objective Response Rate
Description
Objective response rate was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria
Time Frame
Up to 8 weeks
Title
Adverse Events
Description
Adverse events included adverse events using CTCAE Criteria and unplanned surgery delays.
Time Frame
Up to 12 weeks
Title
Disease-free Survival
Description
Disease-free survival was defined as the time from the administration of the first dose to first disease progression or death.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years or above.
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.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
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;
Written informed consent.
Exclusion Criteria:
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.)
Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
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.
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.
With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
With hyperthyroidism, or organic thyroid disease.
With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
History of a clear neurological or psychiatric disorder.
History of drug abuse or alcohol abuse.
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.
Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.
Any other factors that are not suitable for inclusion in this study judged by investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xingchen Peng, Professor
Phone
+8618980606753
Email
pxx2014@scu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xingchen Peng, Professor
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for HNSCC
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