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The Efficacy and Safety of Neoadjuvant Low-dose Radiotherapy Combined With Chemoimmunotherapy in Locally Advanced HNSCC

Primary Purpose

Head and Neck Squamous Cell Carcinoma, Neoadjuvant Treatment

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Low-dose radiotherapy
Sponsored by
Fifth Affiliated Hospital, Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring locally advanced HNSCC, neoadjuvant treatment, low-dose radiotherapy, pathological response rates

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Untreated, histologically confirmed head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx or larynx), staging T3-4N0M0 or T1-4N1-3M0, III-IVB, according to the eighth edition of the AJCC staging system;
  2. Eligible for radical surgery, as judged by surgeons.
  3. Aged ≥ 18 years and ≤ 70 years.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  5. Life expectancy of more than 6 months.
  6. At least one measurable lesion according to RECIST 1.1.
  7. Adequate organ function, based on meeting all of the following criteria (no blood components and cytologic growth factors were received within 14 days prior to the test):

    1. Hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 109/L; and platelet count ≥ 100 × 109/L;
    2. Serum albumin ≥ 28 g/L;
    3. Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN;
    4. Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min;
    5. Activated partial clotting enzyme time and international standardized ratio (INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin with INR within the expected treatment range of anticoagulants can be screened ).

      43/5000

    6. Thyroid Stimulating Hormone (TSH) ≤ULN; If abnormal, T3 and T4 levels should be examined, and patients with normal T3 and T4 levels can be screened.
  8. Women of childbearing age should agree to the use of contraception (e.g., intrauterine devices, birth control pills, or condoms) during drug administration and for 3 months thereafter.
  9. Subjects voluntarily join the study and sign an informed consent form, with good compliance.

Exclusion Criteria (Patients will be excluded if any of the following criteria is met):

  1. Pregnant or lactating women.
  2. A history of allergies to PD-1 inhibitors or any of albumin-bound paclitaxel or cisplatin.
  3. A history of other malignant tumors within the previous 5 years or at the time of enrollment, except for cured skin basal cell carcinoma and cervical in situ cancer, as well as thyroid papilloma.
  4. Uncontrolled cardiac clinical symptoms or diseases, such as :(1) NYHA class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) patients with clinically significant ventricular or ventricular arrhythmias requiring intervention.
  5. Have received any of the following treatments:

    1. Any research drug received prior to the first dose of the current research drug.
    2. Joined another clinical study at the same time, unless it is an observational (noninterventional) clinical study or an intervention during a follow-up.
    3. Needed systemic treatment with corticosteroids (more than 10 mg of prednisone or equivalent per day) or other immunosuppressants within 2 weeks prior to the first dose of the study drug, except for the use of corticosteroids for local inflammation and prevention of allergies or nausea and vomiting. In the absence of active autoimmune diseases, inhalation or partial use of steroids and adrenal corticosteroid replacements at doses greater than 10 mg per day of fentanyl equivalent is permitted.
    4. Live vaccines were administered within 4 weeks prior to the first administration of research drugs.
    5. Major surgery or severe trauma within four weeks of initial use of the study drug.
  6. Serious infections (greater than grade 2 according to the Common Terminology Criteria for Adverse Events), such as severe pneumonia, bacteremia, and infection comorbidities, which required hospitalization, occurred within 4 weeks prior to the first dose of the study drug; baseline chest imaging examinations indicate the presence of active lung inflammation or symptoms and signs of infection within 2 weeks prior to the first dose of the study drug or indicate the need for oral or intravenous antibiotic treatment (excluding the use of preventive antibiotics).
  7. A history of active autoimmune diseases and syndromes (including, but not limited to, interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, and hypothyroidism). Patients with vitiligo or cured childhood asthma/allergies that do not require any intervention in adulthood are not excluded.
  8. A history of immunodeficiency, including HIV-positive status or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation.
  9. Patients with active tuberculosis infection found by history or CT examination, or patients with active tuberculosis infection history within 1 year prior to enrollment, or patients with active tuberculosis infection history before 1 year without formal treatment.
  10. Active hepatitis B (HBV DNA ≥ 2,000 IU/mL or 10,000 copies/mL) or hepatitis C (positive HCV antibody test and HCV RNA above the lower limit of detection).
  11. Known history of psychotropic drug abuse, alcoholism and drug use.
  12. Not suitable for inclusion, as judged by the researcher.

Sites / Locations

  • Fifth Affiliated Hospital of Sun Yat-sen UniversityRecruiting
  • Zhigang LiuRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Low-dose Radiotherapy, Tislelizumab, Combined With Albumin-bound Paclitaxel and Cisplatin

Arm Description

Neoadjuvant therapy will be performed for a total of 2 cycles, with 21 days as a cycle, which includes: ① Low-dose radiotherapy: 1GY/1F, D1, D2, D8, D15, Q3W for two cycles, and the total dose of radiation in the two cycles will be GTV 8 Gy/8 F and GTVnd 8 Gy/8 F; ② Teilizumab: 200 mg D1, Q3W for two cycles; ③ Albumin-bound paclitaxel: 100mg/m2, D1, D8, D15, Q3W for two cycles; ④Cisplatin: 25mg/m2, D1, D8, D15, Q3W for two cycles.

Outcomes

Primary Outcome Measures

Pathological complete response (pCR) rate
the proportion of patients with no residual viable tumor cell under microscope

Secondary Outcome Measures

Major pathological response (MPR) rate
the proportion of patients with the percentage of residual viable tumor cells in the tumor bed less than 10%
Objective Response Rate (ORR)
the proportion of patients with radiographic objective responses (complete response and partial response)
Incidence of treatment-related adverse events
CTCAE 5.0
Non-surgery-delay rate
the proportion of patients with surgical operation conducted more than four weeks longer than scheduled
EORTC QLQ-C30
Quality of life evaluation
EORTC HN35
Quality of life evaluation

Full Information

First Posted
April 13, 2022
Last Updated
December 26, 2022
Sponsor
Fifth Affiliated Hospital, Sun Yat-Sen University
Collaborators
Dongguan People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05343325
Brief Title
The Efficacy and Safety of Neoadjuvant Low-dose Radiotherapy Combined With Chemoimmunotherapy in Locally Advanced HNSCC
Official Title
Neoadjuvant Low-dose Radiotherapy, Tislelizumab, Combined With Albumin-bound Paclitaxel and Cisplatin in Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (NeoRTPC02): an Open Label, Single-arm, Phase II Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 9, 2022 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fifth Affiliated Hospital, Sun Yat-Sen University
Collaborators
Dongguan People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of neoadjuvant low-dose radiotherapy combined with chemoimmunotherapy in resectable locally advanced head and neck squamous cell carcinoma. The eligible patients are scheduled to administered neoadjuvant low-dose radiotherapy, tislelizumab, combined with albumin-bound paclitaxel and cisplatin for two cycles. Radical resection will be performed in 3-4 weeks after two cycles of neoadjuvant therapy. The overall primary study hypothesis is that the novel neoadjuvant combination regime improves the pathological complete response (pCR) rate, with tolerable side effects.

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, Neoadjuvant Treatment
Keywords
locally advanced HNSCC, neoadjuvant treatment, low-dose radiotherapy, pathological response rates

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low-dose Radiotherapy, Tislelizumab, Combined With Albumin-bound Paclitaxel and Cisplatin
Arm Type
Experimental
Arm Description
Neoadjuvant therapy will be performed for a total of 2 cycles, with 21 days as a cycle, which includes: ① Low-dose radiotherapy: 1GY/1F, D1, D2, D8, D15, Q3W for two cycles, and the total dose of radiation in the two cycles will be GTV 8 Gy/8 F and GTVnd 8 Gy/8 F; ② Teilizumab: 200 mg D1, Q3W for two cycles; ③ Albumin-bound paclitaxel: 100mg/m2, D1, D8, D15, Q3W for two cycles; ④Cisplatin: 25mg/m2, D1, D8, D15, Q3W for two cycles.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
Albumin-bound paclitaxel, Cisplatin
Intervention Description
Tislelizumab: 200 mg D1, Q3W for two cycles. Albumin-bound paclitaxel: 100mg/m2, D1, D8, D15, Q3W for two cycles. Cisplatin: 25mg/m2, D1, D8, D15, Q3W for two cycles.
Intervention Type
Radiation
Intervention Name(s)
Low-dose radiotherapy
Intervention Description
Low-dose radiotherapy: 1GY/1F, D1, D2, D8, D15, Q3W for two cycles. The total radiation dose will be GTV 8Gy/8F, GTVnd 8 Gy/8F.
Primary Outcome Measure Information:
Title
Pathological complete response (pCR) rate
Description
the proportion of patients with no residual viable tumor cell under microscope
Time Frame
1 week after surgery
Secondary Outcome Measure Information:
Title
Major pathological response (MPR) rate
Description
the proportion of patients with the percentage of residual viable tumor cells in the tumor bed less than 10%
Time Frame
1 week after surgery
Title
Objective Response Rate (ORR)
Description
the proportion of patients with radiographic objective responses (complete response and partial response)
Time Frame
3-4 weeks after two cycles of neoadjuvant therapy
Title
Incidence of treatment-related adverse events
Description
CTCAE 5.0
Time Frame
from the first day of treatment to 30 days after surgery
Title
Non-surgery-delay rate
Description
the proportion of patients with surgical operation conducted more than four weeks longer than scheduled
Time Frame
8 weeks after two cycles of neoadjuvant therapy
Title
EORTC QLQ-C30
Description
Quality of life evaluation
Time Frame
from 1 week before treatment to 30 days after surgery
Title
EORTC HN35
Description
Quality of life evaluation
Time Frame
from 1 week before treatment to 30 days after surgery
Other Pre-specified Outcome Measures:
Title
Progression-free survival (PFS)
Description
3-year progression free survival rate
Time Frame
from the first day of treatment to the follow up of 3 years
Title
Overall survival (OS)
Description
3-year overall survival rate
Time Frame
from the first day of treatment to the follow up of 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Untreated, histologically confirmed head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx or larynx), staging T3-4N0M0 or T1-4N1-3M0, III-IVB, according to the eighth edition of the AJCC staging system; Eligible for radical surgery, as judged by surgeons. Aged ≥ 18 years and ≤ 70 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Life expectancy of more than 6 months. At least one measurable lesion according to RECIST 1.1. Adequate organ function, based on meeting all of the following criteria (no blood components and cytologic growth factors were received within 14 days prior to the test): Hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 109/L; and platelet count ≥ 100 × 109/L; Serum albumin ≥ 28 g/L; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min; Activated partial clotting enzyme time and international standardized ratio (INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin with INR within the expected treatment range of anticoagulants can be screened ). 43/5000 Thyroid Stimulating Hormone (TSH) ≤ULN; If abnormal, T3 and T4 levels should be examined, and patients with normal T3 and T4 levels can be screened. Women of childbearing age should agree to the use of contraception (e.g., intrauterine devices, birth control pills, or condoms) during drug administration and for 3 months thereafter. Subjects voluntarily join the study and sign an informed consent form, with good compliance. Exclusion Criteria (Patients will be excluded if any of the following criteria is met): Pregnant or lactating women. A history of allergies to PD-1 inhibitors or any of albumin-bound paclitaxel or cisplatin. A history of other malignant tumors within the previous 5 years or at the time of enrollment, except for cured skin basal cell carcinoma and cervical in situ cancer, as well as thyroid papilloma. Uncontrolled cardiac clinical symptoms or diseases, such as :(1) NYHA class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) patients with clinically significant ventricular or ventricular arrhythmias requiring intervention. Have received any of the following treatments: Any research drug received prior to the first dose of the current research drug. Joined another clinical study at the same time, unless it is an observational (noninterventional) clinical study or an intervention during a follow-up. Needed systemic treatment with corticosteroids (more than 10 mg of prednisone or equivalent per day) or other immunosuppressants within 2 weeks prior to the first dose of the study drug, except for the use of corticosteroids for local inflammation and prevention of allergies or nausea and vomiting. In the absence of active autoimmune diseases, inhalation or partial use of steroids and adrenal corticosteroid replacements at doses greater than 10 mg per day of fentanyl equivalent is permitted. Live vaccines were administered within 4 weeks prior to the first administration of research drugs. Major surgery or severe trauma within four weeks of initial use of the study drug. Serious infections (greater than grade 2 according to the Common Terminology Criteria for Adverse Events), such as severe pneumonia, bacteremia, and infection comorbidities, which required hospitalization, occurred within 4 weeks prior to the first dose of the study drug; baseline chest imaging examinations indicate the presence of active lung inflammation or symptoms and signs of infection within 2 weeks prior to the first dose of the study drug or indicate the need for oral or intravenous antibiotic treatment (excluding the use of preventive antibiotics). A history of active autoimmune diseases and syndromes (including, but not limited to, interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, and hypothyroidism). Patients with vitiligo or cured childhood asthma/allergies that do not require any intervention in adulthood are not excluded. A history of immunodeficiency, including HIV-positive status or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation. Patients with active tuberculosis infection found by history or CT examination, or patients with active tuberculosis infection history within 1 year prior to enrollment, or patients with active tuberculosis infection history before 1 year without formal treatment. Active hepatitis B (HBV DNA ≥ 2,000 IU/mL or 10,000 copies/mL) or hepatitis C (positive HCV antibody test and HCV RNA above the lower limit of detection). Known history of psychotropic drug abuse, alcoholism and drug use. Not suitable for inclusion, as judged by the researcher.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhigang Liu, Dr.
Phone
07562526192
Email
liuzhg9@mail.sysu.edu.cn
Facility Information:
Facility Name
Fifth Affiliated Hospital of Sun Yat-sen University
City
Zhuhai
State/Province
Guangdong
ZIP/Postal Code
519000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhigang Liu, Dr.
Phone
07562526192
Email
liuzhg9@mail.sysu.edu.cn
Facility Name
Zhigang Liu
City
Dongguan
ZIP/Postal Code
523059
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhigang Liu
Phone
076928637333
Email
zhigangliu1983@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Efficacy and Safety of Neoadjuvant Low-dose Radiotherapy Combined With Chemoimmunotherapy in Locally Advanced HNSCC

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