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This is an intervention study, aiming to use high and low dose radiotherapy combined with PD-1/PD-L1 inhibitor combined with GM-CSF to observe the effect of anti-tumor immunity and long-term therapeutic response rate, and to explore a new treatment model for patients with advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Recurrent or metastatic advanced head and neck malignancy | Experimental | Patients with a clear pathological diagnosis, imaging diagnosis, and history, no clear recommended standard treatment or inability to tolerate standard treatment, and a clear measurable lesion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GM-CSF | Drug | PD1 antibody is held every three weeks, and GM-CSF is used once every three weeks on days 1-14. Until the patient progresses disease or intolerable toxicity. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | Objective tumor response, including CR and PR, was assessed using RECIST version 1.1. | 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Toxic reaction | Guidelines for Toxicity Management of CTC 5.0 Standard CSCO ESMO irAE. | 36 months |
| Overall survival | The time between enrolment in the study and death from any cause. |
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Inclusion Criteria:
Age ≥18 years old;
Patients with recurrent or metastatic advanced head and neck malignancies (including nasopharyngeal malignancies), with a clear pathological diagnosis, imaging diagnosis, and medical history, no clearly recommended standard treatment regimen or inability to tolerate standard treatment regimens, and clear measurable lesions (>1 cm);
Patients with squamous cell carcinoma who progress after first-line antineoplastic therapy must include a platinum-containing combination chemotherapy or platinum-based concurrent chemoradiotherapy, and patients with secondary resistance after previous anti-PD-1/L1 therapy may also be enrolled;
There is no standard regimen recommended by guidelines after first-line treatment failure in patients with non-squamous cell carcinoma (eg, adenoid cystadenocarcinoma, lung metastases, sarcoma, etc.);
At least one lesion with a diameter of 1 cm to 5 cm (metastases ≥1 cm, if the patient has large metastases, partial tumor irradiation can be allowed) can be treated with radiation therapy at 16 to 24 Gy/2-3Fx doses; Lymph nodes can be used as stand-alone measurable lesions (if lymph nodes are evaluated as an evaluation lesion, they must meet the criteria for target lesions, see RECIST1.1 for definition of a lymph node target lesion);
Patients who have previously received radical radiotherapy need to have an interval of more than 6 months; Patients with an interval of more than 6 months from the previous radiotherapy;
In the past 6 months, there has been no acute coronary syndrome or malignant arrhythmia;
ECOG (Eastern Cooperative Oncology Group), score 0-2, life expectancy assessment ≥ 3 months;
There were no previous severe hematopoietic, cardiac, pulmonary, hepatic, or renal dysfunction or immunodeficiency;
Ejection fraction of cardiac color Doppler ultrasound ≥ 50%;
Myocardial enzyme profile and NT-proBNP do not exceed twice the upper limit of normal;
Troponin and CKMB values do not exceed twice the normal upper limit;
Patients who have had grade 2 or higher AV block in the past six months and need to consider pacemakers will not be included;
Blood pressure hypertension≤ 160mmHg and/or low pressure≤90mmHg. 1 week prior to enrollment, the level of organ function meets the following criteria:
Bone marrow function: hemoglobin ≥ 80g/L, white blood cell count ≥ 3.5*10^9/L or neutrophil count ≥1.5*10^9/L, platelet count ≥ 100*10^9/L, CD8+ T lymphocyte absolute value ≥200/μL; Liver: serum total bilirubin level ≤ 1.5 times the upper limit of normal, when the serum total bilirubin level > 1.5 times the upper limit of normal, direct bilirubin level must ≤ the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal; (5.0 times ≤the upper limit of normal in patients with liver metastases); Kidney: serum creatinine level < 1.5 times the upper limit of normal or creatinine clearance ≥ 50ml/min, urea nitrogen ≤ 200mg/L; serum albumin≥ 30g/L;
Patients must have the ability to understand and voluntarily sign informed consent forms.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiangpan Li, PhD | Contact | +86-027-88041911 | rm001227@whu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Xiangpan Li | Renmin Hospital of Wuhan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Renmin Hospital of Wuhan University | Recruiting | Wuhan | Hubei | 430061 | China |
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| ID | Term |
|---|---|
| D016178 | Granulocyte-Macrophage Colony-Stimulating Factor |
| C000711728 | spartalizumab |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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|
| 36 months |
| Duration of remission | The time from the first confirmed CR or PR to the first occurrence of PD, or to death if it occurs during treatment. | 36 months |
| Disease control rate | Refers to the percentage of cases with CR, PR, and SD (≥4 weeks) in patients with evaluable efficacy. | 36 months |
| Progression-free survival | The time between initial use of the investigational drug and tumor progression/recurrence or death from any cause | 36 months |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |