The Efficacy and Safety of De-escalated Postoperative Radiotherapy in Locally Advanced HNSCC With pCR/MPR

De-escalation of Postoperative Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma With Pathological Complete Response/Major Pathological Response: A Single-arm, Prospective Phase II Clinical Study

This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of de-escalation of postoperative radiotherapy in locally advanced head and neck squamous cell carcinoma with pathological complete response/major pathological response to neoadjuvant therapy. The eligible patients are scheduled to administered postoperative radiotherapy, PTV 50Gy/25F, instead of the standard dose of 60Gy. The overall primary study hypothesis is that reducing the dose of postoperative radiotherapy in the specific population does not affect DFS but significantly reduces treatment related adverse events.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: dose-reduced radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yingpeng Peng, Dr.; Phone Number: 07562526191; Email: pengyp3@outlook.com

Study Locations

• China
  • Guangdong
    • Zhuhai, Guangdong, China, 519000
      • Recruiting
      • Fifth Affiliated Hospital of Sun Yat-sen University
      • Contact: Yingpeng Peng, Dr.; Phone Number: 07562526191; Email: pengyp3@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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; within 6 weeks after receiving neoadjuvant therapy and radical surgery.
2. Pathological evaluation of surgical specimens was pCR (pathologic complete response, no viable tumor cells) or MPR (Major pathologic response, residual viable tumor cells≤10%).
3. Negative surgical margin.
4. No extranodal extension.
5. Aged ≥ 18 years and ≤ 70 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Life expectancy of more than 6 months.

8. 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 ≥ 75 g/L; absolute neutrophil count ≥ 1.5 × 10^9/L; and platelet count ≥ 100 × 10^9/L;
   2. Serum albumin ≥ 25 g/L;
   3. Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN;
   4. Serum creatinine ≤ 1.5 × ULN;
   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 ).
9. Women of childbearing age should agree to the use of contraception (e.g., intrauterine devices, birth control pills, or condoms) during treatment and for 3 months thereafter.
10. The regimen of neoadjuvant therapy can be determined by the clinician.
11. Subjects voluntarily join the study and sign an informed consent form, with good compliance.

Exclusion Criteria:

1. Pregnant or lactating women.
2. 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.
3. Neoadjuvant therapy or radical surgery was not completed.
4. Recurrence or distant metastasis occurred before postoperative radiotherapy.
5. There are contraindications for radiotherapy, chemotherapy, immunotherapy and targeted therapy.
6. Uncontrolled cardiac clinical symptoms or diseases.
7. Serious infections.
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 investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: de-escalation radiotherapy; Postoperative radiotherapy alone	Radiation: dose-reduced radiotherapy; Patients receive 50Gy/25F, 2Gy/F QD, five days a week for 5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	2-year disease free survival rate	from the first day of treatment to the follow up of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	2-year overall survival rate	from the first day of treatment to the follow up of 2 years
Local Relapse Free Survival (LRFS)	2-year local relapse free survival rate	from the first day of treatment to the follow up of 2 years
Distant Metastasis Free Survival (DMFS)	2-year distant metastasis free survival rate	from the first day of treatment to the follow up of 2 years
EORTC QLQ-C30	Quality of life evaluation	from 1 week before treatment to the follow up of 2 years
EORTC HN35	Quality of life evaluation	from 1 week before treatment to the follow up of 2 years
RTOG/EORTC late radiation morbidity scoring scheme	Toxicity criteria of RTOG/EORTC	from 1 week before treatment to the follow up of 2 years

Collaborators and Investigators

• Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2023
• Primary Completion (Anticipated): April 9, 2027
• Study Completion (Anticipated): April 9, 2027

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Estimate): May 11, 2023

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: pathological complete response; major pathological response
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: ZDWY.TJBZLK.002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No