Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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In this exploratory clinical trial, patients with newly diagnosed distant metastatic nasopharyngeal carcinoma were treated with gemcitabine+ cisplatin+PD-1 inhibitor regimen followed by whole-target radiotherapy (IMRT for local regional lesion, SBRT for distant metastasis) and PD-1 inhibitor long-term maintenance regimen. To investigate the efficacy and safety of whole target radiotherapy combined with immuno-maintenance therapy.

Detailed Description
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This exploratory clinical trial will evaluate tumor control rate, survival, and safety of newly diagnosed distant metastatic nasopharyngeal carcinoma by further adding local regional IMRT, distant metastatic SBRT and immuno-maintenance therapy to the standard regimen of gemcitabine+ cisplatin+ PD-1 inhibitor (historical data). To explore whether the full target model can be a better comprehensive therapy for the initial diagnosed distant metastatic nasopharyngeal carcinoma in the era of immunotherapy.

Official Title
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Whole-target Consolidation Therapy After Standard Chemotherapy for Initial Diagnosed Distant Metastatic Nasopharyngeal Carcinoma Under Full-course Immunotherapy: An Open-Label, Single Center, Nonrandomized, Phase 2 Study

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab, gemcitabin, cisplatin
* Radiation: Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female; 18-70 years of age. Had histopathologically confirmed nonkeratinizing metastatic NPC that was diagnosed as stage IVb NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary). Patients who had not received anti-tumor therapy for nasopharyngeal cancer before this clinical trial. Patients evaluated to have a partial response (PR) or stable disease (SD) by head and neck MRI and PET/CT after 3 months of locoregional radiotherapy, and the metastatic lesions were assessed as oligometastatic lesions (the number of total metastatic lesions no more than 5 and the number of metastatic lesions within a single organ no more than 3). Stereotactic body radiotherapy applicable for all metastatic lesions according to MDT. ECOG performance status of 0 or 1. 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 6 months. Exclusion Criteria: 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. CHD no less than grade 2, arrhythmia (QTc interval over 450ms for male and 470ms for female) or cardiac insufficiency. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab Plus Stereotactic Body Radiotherapy<br>Patients were treated with gemcitabine, cisplatin and camrelizumab for 6 cycles, followed by whole-target radiotherapy (IMRT for locoregional lesion and SBRT for oligometastatic lesions) and camrelizumab maintenance therapy. | Drug: Camrelizumab, gemcitabin, cisplatin<br>* Patients receive gemcitabine (1000 mg/m² d1,8), cisplatin (80mg/m² d1), and camrelizumab (200mg, iv drip for over 60min) every 3 weeks for 6 cycles before locoregional radiotherapy.<br>* Other names: PD-1 inhibitor;Radiation: Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy<br>* IMRT: 5 fractions per week for 6 weeks to a total dose of 70 Gy and 33 fractions to the primary tumor. SBRT: 3 months after locoregional IMRT, patients receive SBRT 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. Camrelizumab (200mg, iv drip for over 60min) every 2 weeks began on the first day of IMRT until an intolerable toxicity, or disease progression, or withdrawal of consent, or the investigator determines that he or she has to withdraw from treatment, or has been treated for up to 2 years.<br>* Other names: IMRT;|

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 | 
| 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 years | 
| 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, and 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 | 
| Duration of response (DoR) | Defined as the time from first documentation of objective response to radiological disease progression. | 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