SBRTNCT06722495
Efficacy and Safety of a Third-Course of Neoadjuvant Immunochemotherapy Combined With SBRT in Locally Advanced Head and Neck Squamous Cell Carcinoma Patients With Stable Disease After Two Treatment Courses: A Single-Arm Exploratory Study
A study testing SBRT in people with SBRT and Neoadjuvant Immunochemotherapy, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial summary
Neoadjuvant immunotherapy before surgery has shown good efficacy and safety in locally advanced HNSCC, particularly with the use of PD-1 inhibitors combined with chemotherapy, where some patients have achieved a high rate of pathological complete response. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- SBRT, Neoadjuvant Immunochemotherapy, LA HNSCC
- What is being tested?
- SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 24 Dec 2024to 26 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 and ≤75 years on the date of signing the informed consent form, male or female.
- Histologically and imaging-confirmed T3-4a or N+M0 stage III-IVb (AJCC 8th) HNSCC, patients have received 2-courses of platinum-based chemotherapy and tirilizumab immunotherapy, and whose efficacy is assessed as Stable Disease (SD).
- Life expectancy is at least 3 months.
- ECOG PS 0-1。
- Haematological analysis： 5.1 Absolute neutrophil count (ANC) ≥1.5×10^9/L without granulocyte colony-stimulating factor in the last 14 days； 5.2 Absolute T-lymphocyte value ≥ 0.5 times the lower limit of normal value； 5.3 Platelets ≥100×10^9/L without transfusion or platelet-boosting drugs in the last 14 days； 5.4 Haemoglobin ≥90g/L without transfusion or erythropoietin use in the last 14 days.
- Renal function:
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- 6.1 Creatinine clearance (Ccr) ≥60 mL/min; Ccr will be calculated using the Cockcroft-Gault formula: Ccr = (140-age) × body weight (kg) / [0.818 (0.85 for males, 0.85 for females) × blood creatinine (SCr, umol/L) ] or Ccr = (140-age) × body weight (kg)/ [72 × blood creatinine (SCr, mg/dL) ]; 6.2 Creatinine ≤ 1.5 × upper limit of normal (ULN)； 6.3 Routine urinalysis suggests urinary protein ≤ +; 6.4 Quantitative 24-hour urine protein <1.0g.
- Liver function:
- 7.1 Serum total bilirubin (TBil) ≤ 1.5 × ULN; 7.2 AST and ALT ≤ 2.5 × ULN, ≤ 5 × ULN for liver metastases, and TBil ≤ 3 × ULN.
- Coagulation: international normalised ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
- Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects may be enrolled if total T3 (or FT3) and FT4 are within the normal range.
- Cardiac enzyme profiles within the normal range (enrolment is also permitted if the investigator's combined judgement is that it is a purely laboratory abnormality of no clinical significance).
- Patients must be able to understand and voluntarily sign an informed consent form.
Who cannot join
- Hypersensitivity to any of the antineoplastic therapeutic drug components of this research.
- Those who have previously suffered from other malignant tumours and have received radiotherapy.
- have uncontrolled clinical symptoms or cardiac disease including, but not limited to, symptomatic congestive heart failure (Grade 2 and above as determined by the New York Heart Association's Functional Class), unstable angina pectoris, acute myocardial ischaemia, and poorly controlled cardiac arrhythmias. Past history of myocarditis and cardiomyopathy.
- Active autoimmune disease requiring systemic therapy (e.g., use of disease-mitigating drugs, glucocorticoids, or immunosuppressants). Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy.
- History of (non-infectious) pneumonia requiring steroids or current pneumonia.
- Have active tuberculosis.
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- History of non-infectious pneumonia requiring glucocorticoid therapy within 1 year prior to first dose or current clinically active interstitial lung disease.
- Active or uncontrolled infection requiring systemic therapy.
- History of human immunodeficiency virus (HIV) infection (e.g., HIV-positive).
- Liver disease such as cirrhosis, decompensated liver disease; known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) positive and HBV-DNA > upper limit of normal in the laboratory of the research centre) or active hepatitis C virus infection (e.g., HCV antibody positive and HCV RNA level above the lower limit of detection).
- Note: Hepatitis B subjects meeting the following criteria may also be enrolled: 10.1 HBV viral load <1000 copies/ml (200 IU/ml) prior to the first dose, and subjects should receive anti-HBV therapy throughout the study treatment period to avoid viral reactivation; 10.2 In 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 needed.
- Have an active bleeding disorder or other history of severe bleeding.
- Allogeneic organ transplantation (except corneal transplantation) or allogeneic haematopoietic stem cell transplantation.
- Pregnant or breastfeeding, or preparing to become pregnant during the trial period.
- Medical, psychological, or social condition that may interfere with the subject's participation in the research or affect the assessment of the results; or other conditions that, in the opinion of the investigator, make enrolment inappropriate, or that, in the opinion of the investigator, present other potential risks that make participation in this research inappropriate.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510120
ling Ye, MD, +861 866 608 0933, 32600972@qq.com
Shule Xie, MD, +861 569 243 4749, xieshuleah@163.com
About this study
Neoadjuvant immunotherapy before surgery has shown good efficacy and safety in locally advanced HNSCC, particularly with the use of PD-1 inhibitors combined with chemotherapy, where some patients have achieved a high rate of pathological complete response. However, approximately 40% of patients respond poorly to neoadjuvant immunochemotherapy, with prolonged treatment courses failing to significantly improve outcomes, and some patients may even experience disease progression. For these patients, timely surgery or definitive radiotherapy combined with other well-tolerated therapeutic approaches is needed to improve pathological response rates, enhance long-term survival, and preserve organ function.
Read the detailed description
In recent years, the introduction of PD-1 inhibitors has revolutionized cancer treatment, including head and neck squamous cell carcinoma (HNSCC). Data from The Cancer Genome Atlas (TCGA) shows HNSCC is one of the most immunogenic cancers, linked to immune dysfunction such as impaired immune cell function and antigen presentation defects. Immunotherapy, alone or combined with chemotherapy, has become the standard first-line treatment for recurrent or metastatic HNSCC, as supported by clinical trials like Keynote-040, Keynote-048, and CheckMate 141, which demonstrated improved patient outcomes.
There is also growing interest in neoadjuvant immunotherapy for locally advanced HNSCC. A phase II clinical trial (NCT03174275) showed that neoadjuvant camrelizumab combined with cisplatin and paclitaxel achieved a pathologic complete response (pCR) rate of 37% and a major pathological response (MPR) rate of 74%. Another trial combining PD-1 inhibitor tislelizumab with nab-paclitaxel, platinum, and fluorouracil reported an objective response rate (ORR) of 85.7% and a pCR rate of 42.9%.
In a retrospective analysis of 110 locally advanced oral cavity squamous cell carcinoma (OCSCC) patients treated at our institution, the ORR after two cycles of neoadjuvant immunochemotherapy was 55.4%, with 41% of patients showing stable disease (SD). Further treatment cycles did not improve outcomes for these patients, highlighting the need for alternative treatments for those unresponsive to neoadjuvant therapy.
- Conditions
- SBRT, Neoadjuvant Immunochemotherapy, LA HNSCC
- Being tested
- SBRT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
Patient will receive SBRT (8Gy*3F) in combination with the original regimen of neoadjuvant immunochemotherapy in course 3. Gross tumor target volume (GTV) based on the primary foci clearly identified by clinical and imaging examinations. The GTV was discharged 3 mm to generate a Planning target volume (PTV). the target area (PTV) was dosed accordingly to the PTV.
| Study group | Role | What they receive |
|---|---|---|
| 3-Course of Neoadjuvant Immunochemotherapy combined with SBRT in LA-HNSCC with SD after 2-courses | Experimental | Stereotactic body radiation therapy added between 2-course and 3-course treatment. Receives: Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
Proportion of subjects containing complete response and partial response, i.e., the sum of the diameters of the target lesions is at least 30% smaller compared to baseline, derived from the RECIST v1.1 criteria at 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
Measured: 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
Secondary outcomes (4)
Overall response rate
The percentage of patients with a best overall response of CR or PR relative to the efficacy evaluable population.
Measured: 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
Pathological complete response
No surviving tumor cells are found in a sample of a completely resected tumor.
Measured: 10days after surgery
Major pathologic response
Percentage of residual viable tumor cells ≤10% in samples of completely resected tumors.
Measured: 10days after surgery
Pathological partial response
Percentage of residual viable tumor cells >10%, ≤70% in samples of completely resected tumors.
Measured: 10days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start24 Dec 2024 (estimated)
- Primary completion26 Sep 2026 (estimated)
- Study completion26 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SBRTStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm exploratory clinical study aimed at evaluating the efficacy and safety of combining stereotactic body radiation therapy (SBRT) with subsequent treatments in patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) who are unresponsive to neoadjuvant immunochemotherapy. The study plans to enroll 20 patients diagnosed with stage III-IVb (AJCC 8th) LA HNSCC who have received two cycles of platinum-based chemotherapy and PD-1 inhibitor immunotherapy, but achieved stable disease (SD) according to RECIST 1.1 criteria. These patients will receive SBRT (8Gy\*3F) during the third cycle of immunochemotherapy, followed by standard surgery and postoperative radiotherapy/chemoradiotherapy. The primary endpoint is the objective response rate (ORR) of the primary lesion after the third cycle, with secondary endpoints including overall ORR, pathologic complete response (pCR), major pathologic response (mPR), and partial pathologic response (pPR).
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06722495
- Sponsor's protocol ID
- SYSKY-2024-804-02
- Status last verified
- Dec 2024
- First submitted
- 6 Nov 2024
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of a Third-Course of Neoadjuvant Immunochemotherapy Combined With SBRT in Locally Advanced Head and Neck Squamous Cell Carcinoma Patients With Stable Disease After Two Treatment Courses: A Single-Arm Exploratory Study
- ClinicalTrials.gov ID
- NCT06722495
- Acronym / sponsor ID
- SYSKY-2024-804-02
- Conditions
- SBRT, Neoadjuvant Immunochemotherapy, LA HNSCC
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 24 Dec 2024 (estimated)
- Primary completion
- 26 Sep 2026 (estimated)
- Study completion
- 26 Dec 2026 (estimated)
- First posted
- 9 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neoadjuvant immunotherapy before surgery has shown good efficacy and safety in locally advanced HNSCC, particularly with the use of PD-1 inhibitors combined with chemotherapy, where some patients have achieved a high rate of pathological complete response. However, approximately 40% of patients respond poorly to neoadjuvant immunochemotherapy, with prolonged treatment courses failing to significantly improve outcomes, and some patients may even experience disease progression. For these patients, timely surgery or definitive radiotherapy combined with other well-tolerated therapeutic approaches is needed to improve pathological response rates, enhance long-term survival, and preserve organ function.
Detailed description
In recent years, the introduction of PD-1 inhibitors has revolutionized cancer treatment, including head and neck squamous cell carcinoma (HNSCC). Data from The Cancer Genome Atlas (TCGA) shows HNSCC is one of the most immunogenic cancers, linked to immune dysfunction such as impaired immune cell function and antigen presentation defects. Immunotherapy, alone or combined with chemotherapy, has become the standard first-line treatment for recurrent or metastatic HNSCC, as supported by clinical trials like Keynote-040, Keynote-048, and CheckMate 141, which demonstrated improved patient outcomes.
There is also growing interest in neoadjuvant immunotherapy for locally advanced HNSCC. A phase II clinical trial (NCT03174275) showed that neoadjuvant camrelizumab combined with cisplatin and paclitaxel achieved a pathologic complete response (pCR) rate of 37% and a major pathological response (MPR) rate of 74%. Another trial combining PD-1 inhibitor tislelizumab with nab-paclitaxel, platinum, and fluorouracil reported an objective response rate (ORR) of 85.7% and a pCR rate of 42.9%.
In a retrospective analysis of 110 locally advanced oral cavity squamous cell carcinoma (OCSCC) patients treated at our institution, the ORR after two cycles of neoadjuvant immunochemotherapy was 55.4%, with 41% of patients showing stable disease (SD). Further treatment cycles did not improve outcomes for these patients, highlighting the need for alternative treatments for those unresponsive to neoadjuvant therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm exploratory clinical study aimed at evaluating the efficacy and safety of combining stereotactic body radiation therapy (SBRT) with subsequent treatments in patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) who are unresponsive to neoadjuvant immunochemotherapy. The study plans to enroll 20 patients diagnosed with stage III-IVb (AJCC 8th) LA HNSCC who have received two cycles of platinum-based chemotherapy and PD-1 inhibitor immunotherapy, but achieved stable disease (SD) according to RECIST 1.1 criteria. These patients will receive SBRT (8Gy*3F) during the third cycle of immunochemotherapy, followed by standard surgery and postoperative radiotherapy/chemoradiotherapy. The primary endpoint is the objective response rate (ORR) of the primary lesion after the third cycle, with secondary endpoints including overall ORR, pathologic complete response (pCR), major pathologic response (mPR), and partial pathologic response (pPR).
| Arm | Type | Receives |
|---|---|---|
| 3-Course of Neoadjuvant Immunochemotherapy combined with SBRT in LA-HNSCC with SD after 2-courses | Experimental | Radiation: SBRTStereotactic body radiation therapy added between 2-course and 3-course treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥18 and ≤75 years on the date of signing the informed consent form, male or female.
- Histologically and imaging-confirmed T3-4a or N+M0 stage III-IVb (AJCC 8th) HNSCC, patients have received 2-courses of platinum-based chemotherapy and tirilizumab immunotherapy, and whose efficacy is assessed as Stable Disease (SD).
- Life expectancy is at least 3 months.
- ECOG PS 0-1。
- Haematological analysis： 5.1 Absolute neutrophil count (ANC) ≥1.5×10^9/L without granulocyte colony-stimulating factor in the last 14 days； 5.2 Absolute T-lymphocyte value ≥ 0.5 times the lower limit of normal value； 5.3 Platelets ≥100×10^9/L without transfusion or platelet-boosting drugs in the last 14 days； 5.4 Haemoglobin ≥90g/L without transfusion or erythropoietin use in the last 14 days.
Key exclusion criteria (15 listed)
- Hypersensitivity to any of the antineoplastic therapeutic drug components of this research.
- Those who have previously suffered from other malignant tumours and have received radiotherapy.
- have uncontrolled clinical symptoms or cardiac disease including, but not limited to, symptomatic congestive heart failure (Grade 2 and above as determined by the New York Heart Association's Functional Class), unstable angina pectoris, acute myocardial ischaemia, and poorly controlled cardiac arrhythmias. Past history of myocarditis and cardiomyopathy.
- Active autoimmune disease requiring systemic therapy (e.g., use of disease-mitigating drugs, glucocorticoids, or immunosuppressants). Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy.
- History of (non-infectious) pneumonia requiring steroids or current pneumonia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRTPatient will receive SBRT (8Gy*3F) in combination with the original regimen of neoadjuvant immunochemotherapy in course 3. Gross tumor target volume (GTV) based on the primary foci clearly identified by clinical and imaging examinations. The GTV was discharged 3 mm to generate a Planning target volume (PTV). the target area (PTV) was dosed accordingly to the PTV. | Radiation | 3-Course of Neoadjuvant Immunochemotherapy combined with SBRT in LA-HNSCC with SD after 2-courses |
Primary outcome
Objective response rate
Time frame: 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
Proportion of subjects containing complete response and partial response, i.e., the sum of the diameters of the target lesions is at least 30% smaller compared to baseline, derived from the RECIST v1.1 criteria at 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
4 secondary outcomes
Overall response rate
Time frame: 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.
Pathological complete response
Time frame: 10days after surgery
Major pathologic response
Time frame: 10days after surgery
Pathological partial response
Time frame: 10days after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Guangzhou, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SBRT in people with SBRT and Neoadjuvant Immunochemotherapy, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: 3 weeks after the 3rd course of Neoadjuvant immunochemotherapy + SBRT, including by imaging assessment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.