De-Escalation Postoperative Radiotherapy for Oral Squamous Cell Carcinoma With pCR/MPR.

A Phase II Clinical Study of Continuous Hyperfractionated Accelerated Radiotherapy(CHART) in Oral Cancer Patients Who Underwent Neoadjuvant Chemotherapy Combined With Immunotherapy and Achieved pCR and MPR After Surgery.

The prognosis of locally advanced oral squamous cell carcinoma(OSCC ) is poor, and there are still many problems to be solved in the current treatment paradigm. Neoadjuvant chemotherapy combined with immunotherapy can significantly improve the pCR and MPR rates in patients with locally advanced OSCC. For patients who achieve pCR and MPR after neoadjuvant therapy and surgery, it is still hotly debated regarding whether to implement postoperative de-escalation radiotherapy. Neoadjuvant therapy is an ideal predictor of radiosensitivity. In theory, neoadjuvant therapy can eliminate microscopic lesions, thereby reducing the dose and volume of irradiation.

Continuous hyperfractionated accelerated radiotherapy (CHART, based on hyperfractionated radiotherapy, increasing daily or weekly treatments and shortening the total treatment duration, but reducing the total dose), is to give a higher dose of radiation to tumor tissue in a shorter period of time, so as to overcome the accelerated reproliferation and inhibit the repair of sublethal damage of tumor cells. It is beneficial to improve the local control rate of tumor, control the acute injury of normal tissue and the yield acceptable late treatment-related complications. The specific protocol was as follows: high-risk CTV area (CTV1), 45Gy in total, fraction dose of 1.5Gy, twice a day, bioequivalent dose (BED) of 51.75Gy; Low-risk CTV area(CTV2), 39Gy in total , fraction dose of 1.3Gy, twice a day, BED of 44.07Gy; A total of 30 radiotherapy fraction were performed 10 times a week for 3 weeks.

Study Overview

• Status: Recruiting
• Conditions: De-escalated Radiotherapy; Head and Neck Cancer
• Intervention / Treatment: Radiation: Continuous, hyperfractionated, accelerated radiotherapy(CHART)

• Study Type: Interventional
• Enrollment (Estimated): 103
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bi Zhuofei, Dr.; Phone Number: 13632301621; Email: bizhf@mail.sysu.edu.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Contact: Jialing Wu; Email: wujling7@mail3.sysu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Untreated, histologically confirmed oral cavity carcinoma, staging T2-4N0M0 or T1-4N1-3M0, II-IVB, according to the eighth edition of the AJCC staging system.
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 ≤ 80 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. Life expectancy of more than 6 months.
8. 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.
9. The regimen of neoadjuvant therapy can be determined by the clinician.
10. 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: Continuous hyperfractionated accelerated radiotherapy(CHART)	Radiation: Continuous, hyperfractionated, accelerated radiotherapy(CHART); high-risk CTV area (CTV1), 45Gy in total, fraction dose of 1.5Gy, twice a day, bioequivalent dose (BED) of 51.75Gy; Low-risk CTV area(CTV2), 39Gy in total , fraction dose of 1.3Gy, twice a day, BED of 44.07Gy; A total of 30 radiotherapy fraction were performed 10 times a week for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year PFS	PFS is the time from the initiation of therapy to recurrence or death of any cause.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year OS	OS is defined as the time interval from the beginning of treatment to death.	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 23, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: de-escalated radiotherapy; CHART; head and neck cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: SYSKY-2024-238-01

Drug and device information, study documents

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