Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma
Primary Purpose
Nasopharyngeal Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Camrelizumab, gemcitabin, cisplatin
Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring Oligometastatic Nasopharyngeal Carcinoma, Immunotherapy, Stereotactic Body Radiotherapy
Eligibility Criteria
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.
Sites / Locations
- Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Camrelizumab Plus Stereotactic Body Radiotherapy
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
Adverse events
NCI-CTC5.0 and RTOG standards are adopted, and acute subjective toxicity, acute objective toxicity and late subjective toxicity are included.
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.
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.
Duration of response (DoR)
Defined as the time from first documentation of objective response to radiological disease progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05431764
Brief Title
Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2022 (Anticipated)
Primary Completion Date
June 20, 2025 (Anticipated)
Study Completion Date
June 20, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma
Keywords
Oligometastatic Nasopharyngeal Carcinoma, Immunotherapy, Stereotactic Body Radiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Camrelizumab Plus Stereotactic Body Radiotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab, gemcitabin, cisplatin
Other Intervention Name(s)
PD-1 inhibitor
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy
Other Intervention Name(s)
SBRT, IMRT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Median progression-free survival (PFS)
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Objective response rate is the rate of patients achieving complete response or partial response for a certain period of time after intervention.
Time Frame
2 years
Title
Disease control rate (DCR)
Description
Disease control rate is the rate of patients achieving complete response, partial response or stable disease for at least 4 weeks after intervention.
Time Frame
2 years
Title
Median overall survival (OS)
Description
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
Time Frame
2 years
Title
Adverse events
Description
NCI-CTC5.0 and RTOG standards are adopted, and acute subjective toxicity, acute objective toxicity and late subjective toxicity are included.
Time Frame
2 years
Title
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
Description
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, and after treatment.
Time Frame
2 years
Title
Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
Description
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.
Time Frame
2 years
Title
Duration of response (DoR)
Description
Defined as the time from first documentation of objective response to radiological disease progression.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ming-Yuan Chen, MD, PhD
Phone
86-20-8734-3361
Email
chmingy@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Rui You, MD, PhD
Phone
86-13580439820
Email
yourui@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming-Yuan Chen, MD, PhD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming-Yuan Chen, MD,PhD
Phone
86-20-8734-2422
Email
chmingy@mail.sysu.edu.cn
12. IPD Sharing Statement
Learn more about this trial
Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma
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