Trial Title:
Reduced-dose RT With/Without CCT Versus Standard CCRT for High-risk LANPC Who Achieved CR Post Induction Chemotherapy
NCT ID:
NCT06092957
Condition:
Nasopharyngeal Carcinoma
De-escalation Therapy
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Cisplatin
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:
Cisplatin-based induction chemotherapy
Description:
Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before
radiotherapy including GP, TP, and TPF regimen.
Arm group label:
Induction chemotherapy plus conventional concurrent chemoradiotherapy
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy alone
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy
Intervention type:
Drug
Intervention name:
Full course of PD-1/PD-L1 blockades
Description:
a) Camrelizumab 200mg, b) Toripalimab 240mg, or c) Adebrelimab 1200mg will be started on
day 1 of induction chemotherapy and given every 3 weeks for up to 12 cycles, or until
intolerable toxicity, or disease progression or withdrawal from the treatment.
Arm group label:
Induction chemotherapy plus conventional concurrent chemoradiotherapy
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy alone
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy
Intervention type:
Radiation
Intervention name:
Reduced-dose IMRT
Description:
GTVnx:60Gy/30F/2.0Gy，CTV1:54Gy/30F/1.8Gy，CTV2:48Gy/30F/1.6Gy
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy alone
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy
Intervention type:
Radiation
Intervention name:
Standard-dose IMRT
Description:
GTVnx：69.96Gy/33Fr/2.12Gy；CTV1：60.60Gy/33Fr/1.82y；CTV2：54.12Gy/33Fr/1.64Gy
Arm group label:
Induction chemotherapy plus conventional concurrent chemoradiotherapy
Intervention type:
Drug
Intervention name:
Concurrent Chemotherapy
Description:
Cisplatin 100mg/m2 every 3 weeks for 2 cycles
Arm group label:
Induction chemotherapy plus conventional concurrent chemoradiotherapy
Arm group label:
Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy
Summary:
This prospective trial aims to enroll patients with high-risk stage III-IVA (AJCC 8th,
except T3N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Under the
condition of full course of PD-1/PD-L1 blockades, patients who achieved both radiological
and biological complete response after 3 cycles of platinum-based chemotherapy plus
PD-1/PD-L1 blockades will be randomized in a 1:1:1 ratio to receive reduced-dose
radiotherapy (60Gy/30F) alone or reduced-dose radiotherapy plus concurrent chemotherapy
or standard dose radiotherapy (70Gy/33F) with concurrent chemotherapy. To solve the
urgent problem of whether patients with high-risk advanced nasopharyngeal carcinoma are
suitable for downgrade treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated
or undifferentiated type, i.e., WHO type II or type III).
2. Tumor staged as III-IVA (AJCC 8th, except T3N0).
3. Patients who achieved both radiological and biological CR according to the RECIST
criteria on the basis of MRI, PET-CT and endoscopic biopsy, and EBV DNA load =0
copies/mL (or lower than the test line) after 3 cycles of induction therapy of
platinum-based chemotherapy plus immunotherapy.
4. Eastern Cooperative Oncology Group performance status ≤1.
5. Adequate organ function:
Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet
count ≥100×10e9/L.
Adequate liver and kidney function: Alanine Aminotransferase (ALT)/Aspartate
Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.;
creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the
upper normal limit.
6. Patients must be informed of the investigational nature of this study and give
written informed consent.
Exclusion Criteria:
1. Patients who are evaluated as PR or SD or PD or EBV DNA load of >0 copies/mL after 3
cycles of induction therapy of platinum-based chemotherapy plus PD-1/PD-L1
blockades.
2. The laboratory examination value does not meet the relevant standards within 7 days
before enrollment.
3. Patients have received prior chemotherapy, immunotherapy, targeted therapy, or
surgery (other than diagnostic treatment).
4. Subjects who underwent anti-PD-1 /PD-L1 antibody or anti-CTLA-4 antibody (or any
other antibody acting on T cell synergistic stimulation or checkpoint pathway) and
anti-angiogenic drugs.
5. Active central nervous system (CNS) metastases (indicated by clinical symptoms,
cerebral edema, steroid requirement, or progressive disease).
6. Grade ≥2 epistaxis (defined as the need for medical intervention such as nasal
tamponade, cautery, topical vasoconstrictors, according to CTCAE 5.0) within 1 month
prior to enrollment; Macroscopic hemoptysis or hematemesis) is defined as ≥1/2
teaspoon of bright red blood, or a blood clot with little/no sputum on each cough).
(Patients with mixed sputum-blood occasionally may be enrolled).
7. Patients with hypertension who cannot be reduced to the normal range by
antihypertensive drug treatment (systolic blood pressure > 140 mmHg/diastolic blood
pressure > 90 mmHg), patients with ≥ grade II coronary heart disease, arrhythmia
(including QTc interval prolongation > 450 ms in men and > 470 ms in women) and
cardiac insufficiency.
8. Patients currently take warfarin, heparin, aspirin (> 325 mg/day) or other NSAIDs
known to inhibit platelet function, ticlopidine, clopidogrel, or cilostazol.
(Patients can be enrolled if they discontinue these drugs 10 days prior to the
commence of study and meet the requirements of coagulation in the enrollment
criteria).
9. Patients with other malignancies (except for cervical cancer, basal cell carcinoma
or squamous cell carcinoma of the skin, localized prostate cancer, and ductal
carcinoma in situ who have undergone curative treatment).
10. Has a known history of interstitial lung disease.
11. Known history of hypersensitivity to any components of the PD-1/PD-L1 blockades
formulation or other monoclonal antibodies.
12. Has a known history of allergic reactions to the drugs in the study (gemcitabine,
cisplatin, docetaxel, abraxane, paclitaxel ).
13. Has active autoimmune disease or any condition that requires systemic corticosteroid
or immunosuppressive therapy, 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. Subjects with the following
conditions will not be excluded from this study: asthma that requires intermittent
use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo,
Graves' disease, or Hashimoto's disease. Additional exceptions may be made with
medical monitor approval.
14. Complications requiring long-term use of immunosuppressive drugs or systemic or
local use of immunosuppressive-dose corticosteroids.
15. HIV positive; HBsAg positive and HBV DNA copy number positive (quantitative
detection ≥ 1000 cps/ml); chronic hepatitis C with blood screening positive (HCV
antibody positive).
16. Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB
treatment is ongoing or within 1 year prior to screening.
17. Has received a live vaccine; or a systematic glucocorticoid therapy ; or any
anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) ; any
Chinese anti-tumor herbs within 4 weeks prior to enrollment.
18. Pregnancy or breastfeeding.
19. Other patients who were considered unsuitable by the treating physicians.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 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:
Ming-Yuan Chen, MD,PhD
Start date:
October 9, 2023
Completion date:
October 30, 2031
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Agency class:
Other
Collaborator:
Agency:
Guangdong Provincial People's Hospital
Agency class:
Other
Collaborator:
Agency:
Second Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
The fifth Affiliated Hospital of Guangzhou Medcial University
Agency class:
Other
Collaborator:
Agency:
Zhongshan People's Hospital, Guangdong, China
Agency class:
Other
Collaborator:
Agency:
Hunan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Tongji Hospital
Agency class:
Other
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/NCT06092957
