PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced HNSCC After Neoadjuvant Immunochemotherapy

NCT05980715 | Recruiting Phase 3

• 1 other identifier: SYSKY-2023-463-02
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

Brief 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. 1.Main study endpoint:
2. 2.Secondary study endpoint:

Conditions

HNSCC; Radiotherapy; PD-1

Keywords

HNSCC; radiotherapy; PD-1

Outcome Measures

Primary Outcomes (2)

• Overall survival(OS)

  Overall survival(OS) is the time from day 1 of study treatment(the time randomized) until death from any cause.

  5 years

• The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG

  The incidence(percentage) of late toxicity , Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG.

  5 years

Secondary Outcomes (4)

• Disease-free survival （DFS）

  2 years

• regional recurrence-free survival (RRFS)

  2 years

• distant metastasis free survival (DMFS)

  2 years

• Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG

  2 years

Study Arms (2)

Arm 1（PD-1）

EXPERIMENTAL

Radiotherapy free treatment: the experimental group took PD-1 inhibitor maintenance regimen.

Drug: PD-1inhibitor

Arm 2（radiotherapy）

ACTIVE COMPARATOR

conventional radiotherapy (chemoradiotherapy) regimen, and received comprehensive treatment according to the guidelines (radiotherapy or platinum-based concurrent chemoradiotherapy as stipulated in the guidelines).

Radiation: concurrent chemoradiotherapy

Interventions

PD-1inhibitor DRUG

The PD-1 monoclonal antibody was the same as the neoadjuvant therapy before surgery, and the postoperative level was maintained at Q3\*6.

Arm 1（PD-1）

concurrent chemoradiotherapy RADIATION

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 2（radiotherapy）

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days without the use of granulocyte colony stimulating factor;
• Platelets ≥100×109/L without blood transfusion in the past 14 days;
• Hemoglobin \&gt without blood transfusion or use of erythropoietin within the last 14 days; 9g/dL;
• Total bilirubin ≤1.5× upper limit of normal value (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (ALT or AST ≤5×ULN in patients with liver metastasis);
• Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
• Good coagulation function, defined as International Standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
• 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;
• 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);
• 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;
• 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).

You may not qualify if:

• 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:
• \) HBV viral load \&lt 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:
• 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;
• Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic heart failure;
• 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;
• Poor blood pressure control (systolic \> 140 mmHg, diastolic \> 90 mmHg);
• A history of non-infectious pneumonia requiring glucocorticoid therapy or clinically active interstitial lung disease within 1 year prior to initial administration;

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• First People's Hospital of Foshan: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: collaborator
• Affiliated Cancer Hospital of Shantou University Medical College: collaborator

Study Sites (1)

Sun yat-sen memorial hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Central Study Contacts

Jinsong Li, MD

CONTACT

008618583879908; caobleat@hotmail.com

Haotian Cao, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: August 8, 2023
• Study Start: January 1, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: August 8, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)