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

Official title

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.

Overview

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.

Interventions

• 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.

Primary outcome measures

• 2-year PFS [Time frame: 2 years]

Secondary outcome measures (1)

• 2-year OS [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• 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.
• Pathological evaluation of surgical specimens was pCR (pathologic complete response, no viable tumor cells) or MPR (Major pathologic response, residual viable tumor cells≤10%).
• Negative surgical margin.
• No extranodal extension.
• Aged ≥ 18 years and ≤ 80 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of more than 6 months.
• 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.
• The regimen of neoadjuvant therapy can be determined by the clinician.
• Subjects voluntarily join the study and sign an informed consent form, with good compliance.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen Memorial hospital, Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT06353685 · SYSKY-2024-238-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗