Camrelizumab Plus Stereotactic Body Radiotherapy vs Camrelizumab Alone For Oligometastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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We intend to compare the efficacy and safety of immunotherapy plus stereotactic body radiotherapy at oligometastatic lesions and immunotherapy alone among patients with oligometastatic nasopharyngeal carcinoma whose primary lesion has been well controlled after radical local-regional treatment through this multicenter randomized phase 3 trial.

Detailed Description
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We intend to apply camrelizumab plus stereotactic body radiotherapy at oligometastatic lesions to patients with oligometastatic nasopharyngeal carcinoma whose primary lesion has been well controlled after radical treatment through this multicenter randomized phase 3 trial to investigate whether stereotactic body radiotherapy at oligometastatic lesions on the basis of immunotherapy can achieve clinical cure among a part of patients with distant metastasis and improve their overall survival.

Official Title
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Camrelizumab Plus Stereotactic Body Radiotherapy vs Camrelizumab Alone For Oligometastatic Nasopharyngeal Carcinoma: A Multicenter Randomized Clinical Phase 3 Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: camrelizumab
* Radiation: stereotactic body radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female; 18-70 years of age. Primary lesion and regional lymph nodes completed radical radiotherapy 3 months before stereotactic body radiotherapy and diseases well controlled. Underwent at least first-line systemic chemotherapy, regardless of regimen and curative effect. Imageological evidence for oligometastatic lesions (metastatic tissue biopsy preferred but not necessary). The number of total metastatic lesions no more than 5 and the number of metastatic lesions within a single organ no more than 3. ECOG performance status of 0 or 1. Stereotactic body radiotherapy applicable for all metastatic lesions according to MDT. If metastatic lesions have received local treatment (surgery, radiofrequency ablation, radiotherapy etc.): Eligible if treated lesion is well controlled according to imageological examinations, and the lesion does not need stereotactic body radiotherapy. If treated lesion is not controlled according to imageological examinations: Eligible if the treatment is surgery and that stereotactic body radiotherapy is applicable for the treated lesion. Ineligible if the treatment is radiofrequency ablation or radiotherapy. Maximum diameter of brain metastatic lesion no more than 3cm. Maximum diameter of metastatic lesion (brain excluded) no more than 5cm. Maximum diameter of bone metastatic lesion no more than 6cm if attending doctor decides it is safe to apply the treatment. Life expectancy more than 12 weeks. Exclusion Criteria: Immunotherapy (PD-1/PD-L1 or CTLA-4 monoclonal antibody) failure. CHD no less than grade 2, arrhythmia (QTc interval over 450ms for male and 470ms for female) or cardiac insufficiency. History of severe hypersensitivity to any ingredient of PD-1/PD-L1 or other monoclonal antibody. chemotherapy (cytotoxic or molecular targeted) within 4 weeks before stereotactic body radiotherapy. Imageological evidence for spinal cord compression, or tumor less than 3mm away from spinal cord. Patient with brain metastasis who needs decompression surgery. Other malignancy or malignant hydrothorax. Concurrent known or suspicious autoimmune disease, including dementia and epilepsy. Use of large dose corticosteroids within 4 weeks before study drug administration. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Active tuberculosis (TB), anti-TB treatment is ongoing or within 1 year prior to screening Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive. Received any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment. Pregnancy or lactation. Other ineligible patients according to attending doctor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab Plus Stereotactic Body Radiotherapy<br>Patients receive camrelizumab(200mg, iv drip for over 60min) every 2 weeks from 2 weeks before radiotherapy, and then receive stereotactic body radiotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, investigator decision or the upper limit of treatment duration of 1 year. | Drug: camrelizumab<br>* Patients receive camrelizumab(200mg, iv drip for over 60min) every 2 weeks from 2 weeks before radiotherapy<br>Radiation: stereotactic body radiotherapy<br>* Patients receive stereotactic body radiotherapy for all oligometastatic lesions as radical therapy to control the disease and reduce any potential adverse impact to living quality. The dosage is based on published clinical studies.<br>* Other names: SBRT;|
| Active Comparator: Camrelizumab<br>Patients receive camrelizumab(200mg, iv drip for over 60min) every 2 weeks until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, investigator decision or the upper limit of treatment duration of 1 year. | Drug: camrelizumab<br>* Patients receive camrelizumab(200mg, iv drip for over 60min) every 2 weeks from 2 weeks before radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median progression-free survival (PFS) | Progression-free survival is calculated from the date of randomization to the date of death of any cause or the first progress at any site, censored on the last date of tumor evaluation if no progress has happened. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate is the rate of patients achieving complete response or partial response for a certain period of time after intervention. | 2 years | 
| Disease control rate (DCR) | Disease control rate is the rate of patients achieving complete response, partial response or stable disease for at least 4 weeks after intervention. | 2 years | 
| Clinical benefit rate (CBR) | Clinical benefit rate is the rate of patients achieving complete response, partial response or stable disease for at least 6 months after intervention. | 2 years | 
| Median overall survival (OS) | Overall survival is calculated from the date of randomization to the date of death of any cause, censored on the last date of known survival if no death has happened. | 2 years | 
| Adverse events | NCI-CTC5.0 and RTOG standards are adopted, and acute subjective toxicity, acute objective toxicity and late subjective toxicity are included. | 2 year | 
| Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) | Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment. | 2 years | 
| Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) | Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment. | 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligometastatic Nasopharyngeal Carcinoma, Immunotherapy, Stereotactic Body Radiotherapy