Trial Title:
Reduced-dose Radiotherapy for Stage III Nasopharyngeal Carcinoma Based on the Treatment Response
NCT ID:
NCT06239727
Condition:
Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Cisplatin
Gemcitabine
Capecitabine
Antibodies
Antibodies, Blocking
Conditions: Keywords:
Radiotherapy
Dose
PD-1
Immune Checkpoint Inhibitor
Capecitabine
Quality of Life
Personalised Therapy
Complication
Deintensification
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PD-1 blocking antibody
Description:
1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 200 mg, day 1; start
on day 1 of the first cycle IC and continue every 3 weeks for 3 cycles till the end
of IC.
2. Adjuvant PD-1 blocking antibody: every 3 weeks × 9 cycles; 200 mg, day 1.
Arm group label:
Conventional-dose radiotherapy group
Arm group label:
Not-enrolled population
Arm group label:
Reduced-dose radiotherapy group
Other name:
Camrelizumab
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3
cycles.
Arm group label:
Conventional-dose radiotherapy group
Arm group label:
Not-enrolled population
Arm group label:
Reduced-dose radiotherapy group
Other name:
GEM
Intervention type:
Drug
Intervention name:
Cisplatin (80 mg/m2)
Description:
Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3
cycles.
Arm group label:
Conventional-dose radiotherapy group
Arm group label:
Not-enrolled population
Arm group label:
Reduced-dose radiotherapy group
Other name:
DDP
Intervention type:
Radiation
Intervention name:
Reduced-dose Intensity-modulated radiotherapy
Description:
1. Definitive IMRT, 30 fractions, 5 fractions/week, 1 fraction/day
2. Radiotherapy dose: pGTV: 6360cGy/30F; pCTV1: 5460cGy/30F; pCTV2: 4920cGy/30F.
Arm group label:
Reduced-dose radiotherapy group
Other name:
Reduced-dose IMRT
Intervention type:
Radiation
Intervention name:
Conventional-dose Intensity-modulated radiotherapy
Description:
1. Definitive IMRT, 33 fractions, 5 fractions/week, 1 fraction/day
2. Radiotherapy dose: pGTV: 6996cGy/33F; pCTV1: 6006cGy/33F; pCTV2: 5412cGy/33F.
Arm group label:
Conventional-dose radiotherapy group
Arm group label:
Not-enrolled population
Other name:
Conventional-dose IMRT
Intervention type:
Drug
Intervention name:
Cisplatin (100 mg/m2)
Description:
Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2
cycles
Arm group label:
Conventional-dose radiotherapy group
Arm group label:
Not-enrolled population
Arm group label:
Reduced-dose radiotherapy group
Other name:
DDP
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Metronomic adjuvant capecitabine chemotherapy: 650 mg/m2 p.o. bid, 1 year, adminstration
starts immediately after concurrent chemoradiotherapy.
Arm group label:
Not-enrolled population
Summary:
This is an Open Label, Non-Inferiority, Multicenter, Randomized Phase 3 Trial aimed to
investigate the impact of reduced-dose radiotherapy in combination with chemotherapy and
immunotherapy on patients' prognosis and complication compared with conventional-dose
radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive
stage III NPC patients screened out according to the treatment response.
Detailed description:
The goals of this clinical trial includes: ① To confirm whether LRRFS after reduced-dose
radiotherapy in combination with chemotherapy and immunotherapy is non-inferior to LRRFS
after conventional-dose radiotherapy in combination with chemotherapy and immunotherapy
for treatment-sensitive stage III NPC patients screened out according to the treatment
response; ② To explore the impact of reduced-dose radiotherapy on 3-year OS, 3-year PFS,
3-year DMFS, 3-year LRFS and 3-year RRFS for treatment-sensitive stage III NPC patients
screened out according to the treatment response; ③ To explore the impact of reduced-dose
radiotherapy on radiotherapy complications and quality of life; ④ To explore the
interaction between different clinical factors and the impact of reduced-dose
radiotherapy on the prognosis of patients; ⑤ To explore the biomarkers of sensitivity to
chemotherapy and radiotherapy for patients with nasopharyngeal carcinoma and the
underlying mechanism.
For these purposes, we plan to prospectively enroll stage III NPC patients from 9
hospitals in China. The participants will receive 3 cycles of induction chemotherapy (GP
regimen + Camrelizumab) followed by intensity-modulated radiation therapy. 2 cycles of
concurrent chemotherapy will be administered during the radiotherapy. Patients' treatment
response will be evaluated with MRI examination after 27 fractions of radiotherapy. If
the treatment response after 27 fractions of radiotherapy is complete remission, the
participants will be randomized into reduced-dose radiotherapy group and
conventional-dose radiotherapy group. If the treatment response after 27 fractions of
radiotherapy is not complete remission, the participants will be assigned to the
unenrolled group. All the participants in the unenrolled group will receive
conventional-dose radiotherapy. After the radiotherapy, all the participants will receive
9 cycles of Camrelizumab immunotherapy. Besides, all the participants in the unenrolled
group will also receive metronomic adjuvant capecitabine chemotherapy for 1 year. The
prognosis, complication, and quality of life will be compared between the reduced-dose
radiotherapy group and the conventional-dose radiotherapy group.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age: 18 Years to 65 Years;
2. Eastern Cooperative Oncology Group performance status ≤1;
3. Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma,
the pathological type is non-keratinising carcinoma;
4. Tumor staged as Stage III (AJCC 8th);
5. Patients' lymph node without adverse features (no central necrosis, no muscle/skin
invasion, no lymph node fusion);
6. Normal bone marrow function: white blood cell count > 4×10^9/L, hemoglobin > 90g/L,
platelet count > 100×10^9/L;
7. Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal
(ULN), alanine transaminase and aspartate transaminase ≤ 2.5 × ULN, alkaline
phosphatase ≤ 2.5 × ULN, creatinine clearance rate ≥ 60 ml/min;
8. Receive 3 cycles of indction chemotherapy (GP regimen + Camrelizumab);
9. Plasma EBV DNA after the second cycle of concurrent chemotherapy: 0;
10. Complete remission after 27 fractions of radiotherapy based on the MRI examination
of the nasopharynx and neck (According to Response Evaluation Criteria in Solid
Tumors 1.1);
11. Patients must sign informed consent and be willing and able to comply with the
requirements of visits, treatment, laboratory tests and other research requirements
stipulated in the research schedule;
12. Subjects with pregnancy ability must agree to use reliable contraceptive measures
from screening to 1 year after treatment.
Exclusion Criteria:
1. Hepatitis B virus surface antigen (HBsAg) positive and Hepatitis B virus DNA > 1000
copies/ml;
2. Anti-hepatitis C virus positive;
3. Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune
deficiency syndrome (AIDS);
4. Active tuberculosis: active tuberculosis in the past 1 year should be excluded
regardless with treatment, history of active tuberculosis over 1 year should be
excluded except that previous regulatory anti-tuberculosis treatment is proved;
5. Active, known or suspected autoimmune disease (including but not limited to uveitis,
enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism,
hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes
mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders
requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
6. Previous interstitial lung disease or pneumonia requiring oral or intravenous
steroid therapy;
7. Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg
prednisone per day) or any other form of immunosuppressive therapy. Subjects who
used inhaled or topical corticosteroids were eligible;
8. Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2), 2)
unstable angina, 3) myocardial infarction in past 1 year, 4) supraventricular or
ventricular arrhythmia requiring treatment or intervention;
9. Active infection requiring systemic treatment;
10. Previous or concurrent with other malignant tumors, except for adequately treated
non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
11. History of radiotherapy, except for non-melanoma skin cancer located outside the
target volume of radiotherapy for nasophayngeal carcinoma;
12. Receive treatment for the local or regional disease other than that specified in the
research plan;
13. Pregnant or lactating women (pregnancy test should be considered for women with
sexual life and fertility);
14. Allergy to macromolecular protein preparations, or any component of Camrelizumab;
15. Receiving live vaccine within 30 days of the initial Camrelizumab;
16. Contraindications to MRI examination, for example: claustrophobia, allergy to MRI
contrast;
17. History of psychotropic disease, alcoholism or drug abuse, and other situation
assessed by the investigators that may compromise the safety or compliance of
patients, such as serious disease requiring timely treatment (including mental
illness), severe laboratory abnormalities, or family-social risk factors.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Jun Ma
Phone:
+862087343469
Email:
majun2@mail.sysu.edu.cn
Contact backup:
Last name:
Kaibin Yang
Phone:
+8613725368062
Email:
yangkb@sysucc.org.cn
Investigator:
Last name:
Jun Ma
Email:
Principal Investigator
Investigator:
Last name:
Kaibin Yang
Email:
Sub-Investigator
Facility:
Name:
Zhongshan city Peaple's Hospital
Address:
City:
Zhongshan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Feng Lei
Phone:
+8618933345282
Facility:
Name:
Cancer Hospital of Guangxi Medical University
Address:
City:
Nanning
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiao-Dong Zhu, MD
Email:
zhuxiaodong83@163.com
Facility:
Name:
Cancer Hospital of Guizhou Medical University
Address:
City:
Guiyang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Feng Jin, MD
Email:
jinf8865@yeah.net
Facility:
Name:
Hubei Province Cancer Hosiptal
Address:
City:
Wuhan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
De-Sheng Hu, M.D.
Email:
hds_005@163.com
Facility:
Name:
Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Bian Wu, MD
Email:
bianwu@hust.edu.cn
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ya-Qian Han
Email:
hanyaqiancs@163.com
Facility:
Name:
Xiangya Hospital Central South University
Address:
City:
Changsha
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Liang-Fang Shen, MD
Email:
slf1688@sina.com
Start date:
March 1, 2024
Completion date:
February 20, 2030
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06239727
