Trial Title:
PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced HNSCC After Neoadjuvant Immunochemotherapy
NCT ID:
NCT05980715
Condition:
HNSCC
Radiotherapy
PD-1
Conditions: Official terms:
Squamous Cell Carcinoma of Head and Neck
Immune Checkpoint Inhibitors
Conditions: Keywords:
HNSCC
radiotherapy
PD-1
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PD-1inhibitor
Description:
The PD-1 monoclonal antibody was the same as the neoadjuvant therapy before surgery, and
the postoperative level was maintained at Q3*6.
Arm group label:
Arm 1（PD-1）
Intervention type:
Radiation
Intervention name:
concurrent chemoradiotherapy
Description:
According to the guidelines, concurrent chemoradiotherapy is required, and carboplatin
(50mg/m2) plus concurrent radiotherapy or cisplatin (30mg/m2) plus concurrent
radiotherapy is optional.
Arm group label:
Arm 2（radiotherapy）
Summary:
In patients with locally advanced head and neck squamous cell carcinoma undergoing
standard surgical treatment after neoadjuvant immunochemotherapy, can PD-1 inhibitor
therapy be used instead of adjuvant radiotherapy for both primary and lymph node
pathology? To provide further evidence-based medical evidence for the late precision
treatment of HNSCC patients after neoadjuvant immunochemotherapy. Avoid the side effects
caused by excessive radiotherapy, especially avoid the occurrence of second primary
cancer, radiation osteonecrosis and other diseases.
1. Main study endpoint:
A randomized controlled, non-inferiority, multicentre Phase III trial was conducted
to investigate the difference in 5-year overall survival (OS) between experimental
group (Group B) and control group (group A) in patients undergoing standard surgical
treatment after neoadjuvant immunochemotherapy for locally advanced HNSCC, with both
primary and lymph node pathology revealed by pCR. At the same time, adverse events
and safety were evaluated according to NCI-CTCAE 5.0 criteria and RTOG later
radiotherapy damage evaluation criteria.
Safety indicators focused on late radiotherapy toxicity and the incidence of grade 3
and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG. The differences in the incidence
of grade 3 and 4 adverse events were compared between the experimental group and the
control group.
2. Secondary study endpoint:
The differences in 2-year disease-free survival (DFS), regional relapse-free survival
(RRFS), distant metastasis free survival (DMFS), safety and adverse events were compared.
Safety evaluation NCI-CTC AE 5.0 standard was used to evaluate the acute safety index of
radiotherapy, and RTOG late-stage damage evaluation standard was used to evaluate the
late-stage safety index of radiotherapy.
4) Exploratory goals The influence of prognostic laboratory indicators, clinical risk
factors were analyzed. To explore the factors that influence the efficacy of
radiotherapy after pCR immunotherapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- In this study, patients with locally advanced head and neck squamous cell carcinoma
(AJCC 8th) who underwent standard surgical treatment after neoadjuvant
immunochemotherapy and showed pCR in both primary lesions and lymph node pathology
were selected. Locally advanced squamous cell carcinoma of head and neck includes:
i) T3, N0, M0; 2) T1-T3, N1-N2, M0; 3) T4a, N0-2, M0.
- No history of other malignant tumors
- Ages 18-65
- Normal baseline inspection:
1. The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14
days without the use of granulocyte colony stimulating factor;
2. Platelets ≥100×109/L without blood transfusion in the past 14 days;
3. Hemoglobin > without blood transfusion or use of erythropoietin within the
last 14 days; 9g/dL;
4. Total bilirubin ≤1.5× upper limit of normal value (ULN);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN
(ALT or AST ≤5×ULN in patients with liver metastasis);
6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by
Cockcroft-Gault formula) ≥60 ml/min;
7. Good coagulation function, defined as International Standardized ratio (INR) or
prothrombin time (PT) ≤1.5 times ULN;
8. Normal thyroid function, defined as thyroid stimulating hormone (TSH) within
the normal range. Subjects whose baseline TSH is outside the normal range can
be enrolled if total T3 (or FT3) and FT4 are within the normal range;
9. The myocardial enzyme profile was within the normal range (if the researchers
comprehensively judged that the simple laboratory abnormality was not
clinically significant, it was also allowed to be included);
10. For female subjects of childbearing age, a urine or serum pregnancy test should
be tested negative within 3 days prior to receiving the first study drug
administration (day 1 of Cycle 1). If the urine pregnancy test results cannot
be confirmed negative, a blood pregnancy test is requested. Women of
non-reproductive age were defined as at least one year after menopause or
having undergone surgical sterilization or hysterectomy;
11. If there is a risk of conception, all subjects (male or female) shall use
contraception with an annual failure rate of less than 1% for the entire
duration of treatment up to 120 days after the last study drug administration
(or 180 days after the last chemotherapeutic drug administration).
5 Sign informed consent
Exclusion Criteria:
- 1 HNSCC is not the initial diagnosis of other malignant tumors or neoadjuvant
therapy.
- Prior to treatment An active autoimmune immune disease requiring systemic therapy
(e.g. the use of disease-modifying drugs, glucocorticoids, or immunosuppressants)
has occurred in the last 2 years. Alternative therapies (such as thyroxine, insulin,
or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not
considered systemic therapy;
- Known allogeneic organ transplantation (except corneal transplantation) or
allogeneic hematopoietic stem cell transplantation;
- Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody
positive);
- Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number
detected greater than the upper limit of normal value in the laboratory of the study
center);
Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
1) HBV viral load < before initial administration; At 1000 copies /ml (200 IU/ml),
subjects should receive anti-HBV therapy to avoid viral reactivation throughout the
study treatment period 2) For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-),
and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close
monitoring of viral reactivation is required
- Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the
lower limit);
- Pregnant or lactating women;
- The presence of any serious or uncontrolled systemic disease, such as:
1. The resting electrocardiogram (ECG) presents significant and severely
uncontrollable abnormalities in rhythm, conduction or morphology, such as
complete left bundle branch block, Ⅱ degree or above heart block, ventricular
arrhythmia or atrial fibrillation;
2. Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic
heart failure;
3. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction,
unstable angina pectoris, cerebrovascular accident or transient ischemic
attack, occurred within 6 months before treatment;
4. Poor blood pressure control (systolic > 140 mmHg, diastolic > 90 mmHg);
5. A history of non-infectious pneumonia requiring glucocorticoid therapy or
clinically active interstitial lung disease within 1 year prior to initial
administration;
6. Active pulmonary tuberculosis;
7. There is an active or uncontrolled infection that requires systemic treatment;
8. Clinically active diverticulitis, abdominal abscess, gastrointestinal
obstruction;
9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic
active hepatitis;
10. Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);
11. Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein
quantity > 1.0 g;
12. Patients with mental disorders and unable to cooperate with treatment;
- Medical history or evidence of disease that may interfere with test results, prevent
subjects from fully participating in the study, abnormal values of treatment or
laboratory tests, or other conditions that the investigator considers unsuitable for
enrollment. The investigator considers other potential risks unsuitable for
participation in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun yat-sen memorial hospital
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Haotian Cao, MD
Phone:
008618583879908
Email:
caobleat@hotmail.com
Contact backup:
Last name:
Jinsong Li, MD
Start date:
January 1, 2023
Completion date:
December 31, 2030
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
First People's Hospital of Foshan
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Agency class:
Other
Collaborator:
Agency:
Affiliated Cancer Hospital of Shantou University Medical College
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05980715
