Nasopharyngeal Carcinoma
Conditions
Keywords
Oligometastatic Nasopharyngeal Carcinoma, Immunotherapy, Stereotactic Body Radiotherapy
Brief summary
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
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.
Interventions
DRUGCamrelizumab, gemcitabin, cisplatin
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.
RADIATIONStereotactic Body Radiotherapy, Intensity modulated-radiotherapy
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female; 18-70 years of age. 2. Had histopathologically confirmed nonkeratinizing metastatic NPC that was diagnosed as stage IVb NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary). 3. Patients who had not received anti-tumor therapy for nasopharyngeal cancer before this clinical trial. 4. 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). 5. Stereotactic body radiotherapy applicable for all metastatic lesions according to MDT. 6. ECOG performance status of 0 or 1. 7. Maximum diameter of brain metastatic lesion no more than 3cm. 8. 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. 9. Life expectancy more than 6 months.
Exclusion criteria
1. History of severe hypersensitivity to any ingredient of PD-1/PD-L1 or other monoclonal antibody. 2. chemotherapy (cytotoxic or molecular targeted) within 4 weeks before stereotactic body radiotherapy. 3. Imageological evidence for spinal cord compression, or tumor less than 3mm away from spinal cord. 4. Patient with brain metastasis who needs decompression surgery. 5. Other malignancy or malignant hydrothorax. 6. Concurrent known or suspicious autoimmune disease, including dementia and epilepsy. 7. CHD no less than grade 2, arrhythmia (QTc interval over 450ms for male and 470ms for female) or cardiac insufficiency. 8. Use of large dose corticosteroids within 4 weeks before study drug administration. 9. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. 10. Active tuberculosis (TB), anti-TB treatment is ongoing or within 1 year prior to screening 11. 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. 12. 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. 13. Received any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment. 14. Pregnancy or lactation. 15. Other ineligible patients according to attending doctor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median progression-free survival (PFS) | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | 2 years | Disease control rate is the rate of patients achieving complete response, partial response or stable disease for at least 4 weeks after intervention. |
| Median overall survival (OS) | 2 years | 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 |
| Adverse events | 2 years | NCI-CTC5.0 and RTOG standards are adopted, and acute subjective toxicity, acute objective toxicity and late subjective toxicity are included. |
| Objective response rate (ORR) | 2 years | Objective response rate is the rate of patients achieving complete response or partial response for a certain period of time after intervention. |
| Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) | 2 years | 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. |
| Duration of response (DoR) | 2 years | Defined as the time from first documentation of objective response to radiological disease progression. |
| Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) | 2 years | Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, and after treatment. |
Countries
China
Contacts
Primary ContactMing-Yuan Chen, MD, PhD
Backup ContactRui You, MD, PhD
Outcome results
None listed