SBRT Combined With PD-1 Antibody and Chemotherapy in Oligometastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a multicenter, single-arm, phase II clinical trial. The purpose of this study is to evaluate the efficacy and adverse effect of SBRT combined with programmed death 1 (PD-1) antibody and chemotherapy in nasopharyngeal carcinoma patients with oligometastasis.

Official Title
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SBRT Combined With Programmed Death 1 (PD-1) Antibody and Chemotherapy in Nasopharyngeal Carcinoma With Oligometastasis: A Prospective, Multicenter, Single-arm, Phase II Clinical Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: SBRT
* Drug: Camrelizumab
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as metastatic NPC with no more than 3 metastatic lesions; Histopathological diagnosis of NPC; ECOG 0-1 point; Has not received prior systemic treatment, such as radiotherapy, chemotherapy, immunotherapy or biotherapy; No contraindications to immunotherapy and chemoradiotherapy; Every metastatic lesions could receive SBRT safely; Subject must have a measurable target lesion based on RECIST v1.1; Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L; Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN; Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula); Take effective contraceptions during and three months after treatment; Patients must be informed of the investigational nature of this study and give written informed consent. Exclusion Criteria: Allergic to monoclonal antibodies, any PD-1 antibody components, gemcitabine and cisplatin; Unexplained fever > 38.5 ℃, except for tumor fever; Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy); Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive; Have previously treated with PD-1 antibody or other immunotherapy for PD-1/PD-L1 pathway; Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment; Have known allergy to large molecule protein products or any compound of study therapy; Pregnant or breastfeeding; Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma; Have received a live vaccine within 30 days of planned start of study therapy Has psychiatric drug or substance abuse disorders that would interfere with cooperation with the requirements of the trial; Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT+PD-1+Chemotherapy<br>Patients will receive SBRT first, then PD-1 antibody (Camrelizumab 200mg/Q3W) and chemotherapy (cisplatin 80mg/m2 on d1, gemcitabine 1000mg/m2, d1 and d8, Q3W, maximum 6 cycles), followed by Camrelizumab (200mg/Q3W) until progressive disease, intolerable toxicity, withdrawal of consent or a maximum of 1 year treatment. | Radiation: SBRT<br>* SBRT for metastatic lesions<br>Drug: Camrelizumab<br>* Maximum 6 cycles for combined therapy. Camrelizumab maintenance for 1 year.<br>* Other names: SHR-1210;Drug: Gemcitabine<br>* Maximum 6 cycles for combined therapy.<br>Drug: Cisplatin<br>* Maximum 6 cycles for combined therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Defined as the time from randomization to the first occurrence of disease progression as determined according to RECIST v1.1 or death from any cause, whichever occurs first. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from randomization to death from any cause. | up to 12 months | 
| Objective Response Rate | The percentage of patients with CR and PR assessed according to RECIST v1.1. | up to 12 months | 
| Disease Control Rate | The proportion of patients who have achieved complete response, partial response and stable disease according to RECIST v1.1. | up to 12 months | 
| Adverse Events | All adverse event or serious adverse event that occurred during the study period according to CTCAE v 4.03 | up to 12 months | 
| QoL | Assessed by EQ-5D-5L questionnaire | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBRT, PD-1 antibody, Chemotherapy, Efficacy, Safety, Oligometastasis