Trial Title:
GP Plus Adebrelimab Versus GP Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma
NCT ID:
NCT06455410
Condition:
Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GP
Description:
gemcitabine + cisplatin
Arm group label:
GP combined with adebrelimab neoadjuvant therapy+CCRT
Arm group label:
GP neoadjuvant therapy+CCRT
Intervention type:
Drug
Intervention name:
Adebrelimab
Description:
a PD-L1 inhibitor
Arm group label:
GP combined with adebrelimab neoadjuvant therapy+CCRT
Intervention type:
Drug
Intervention name:
concurrent chemoradiotherapy (CCRT)
Description:
concurrent chemoradiotherapy (CCRT)
Arm group label:
GP combined with adebrelimab neoadjuvant therapy+CCRT
Arm group label:
GP neoadjuvant therapy+CCRT
Summary:
The purpose of this study is to explore the efficacy and safety of neoadjuvant GP
chemotherapy plus adebrelimab versus neoadjuvant GP chemotherapy in treating high-risk
locoregionally advanced nasopharyngeal carcinoma patients.
Detailed description:
Platinum-based neoadjuvant chemotherapy plus concurrent chemoradiotherapy (CCRT) is the
standard of care for patients with locoregionally advanced nasopharyngeal carcinoma
(NPC). Gemcitabine plus cisplatin(GP) has been demonstrated an effective chemotherapy
regimen for NPC patients in previous studies. Three cycles of GP neoadjuvant chemotherapy
resulted in 10% of complete response rate, and GP neoadjuvant chemotherapy added to
chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and
overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as
compared with concurrent chemoradiotherapy alone. Therefore, GP has been established as
the highest level of evidence-based neoadjuvant chemotherapy regimen in the 2020 National
Comprehensive Cancer Network (NCCN) guidelines. Recently, immune checkpoint inhibitors,
such as anti-programmed cell death-1 (PD-1) monoclonal antibody has shown promising
efficacy in NPC patients. Clinical trials have shown objective response rates of
20.5%-34% in patients with recurrent or metastatic NPC patients receiving anti PD-1
monoclonal antibody immunotherapy including pembrolizumab, nivolumab, camrelizumab, and
toripalimab. GP chemotherapy combined with anti PD-1 antibody were hence considered in
treating locoregionally advanced NPC. Concurrent radiotherapy might cause T-cell
dysfunction, and larger-volume elective nodal irradiation might hinder immunotherapy
effects by directly depleting memory T cells. No survival benefit was observed when PD-1
blockade was added concurrently to the CCRT phase for treating head and neck cancers. On
the contrary, several studies have demonstrated that administration of immunotherapy in
the neoadjuvant setting modified the primary tumor into an antigen source for T-cell
expansion and priming, thereby resulting in stronger effects than those of adjuvant
therapy. Currently there were 3 trials exploring the addition of immunotherapy to
chemoradiotherapy, the preliminary results of which were recently published. These trials
had different trial designs, with two trials utilized anti PD-1 inhibitors in all
treatment phases including neoadjuvant, concurrent and adjuvant phases, The third trial,
which was conducted by our team, gave anti PD-1 inhibitor only in the neoadjuvant phase,
and promising efficacy was observed in our study.
Adebrelimab is a recombinant humanized IgG4 monoclonal antibody with specificity for
PD-L1. In a phase III clinical trial of extensive stage small-cell lung cancer, the
addition of adebrelimab significantly improved the median overall survival compared with
the control group (15.3 vs. 12.8，HR 0.72, P=0.0017). So we hypothesize that GP
neoadjuvant chemotherapy combined with adebrelimab could further improve the survival of
patients with high-risk locoregionally advanced NPC (diagnosed with T4 or N2-3 disease).
Therefore, we designed this phase II multi-center randomized controlled trial to evaluate
whether GP neoadjuvant chemotherapy combined with adebrelimab plus cisplatin-based CCRT
improve the complete response rate of high-risk locoregionally advanced NPC patients
compared with GP neoadjuvant chemotherapy plus CCRT.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must be informed of the investigational nature of this study and give
written informed consent.
2. Age ≥ 18 years and ≤65 years, men or non-pregnant women.
3. Patients with histologically confirmed Nonkeratinizing carcinoma of the nasopharynx
(differentiated or undifferentiated type, WHO II or III).
4. Tumor staged as T4N0-1M0 or T1-4N2-3M0 (AJCC 8th).
5. No previous anti-tumor treatment.
6. Eastern Cooperative Oncology Group (ECOG) score 0 or 1.
7. Adequate marrow function: White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥
90g/L, Platelet count ≥100×109/L.
8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total
bilirubin (TBIL) ≤2×upper limit of normal (ULN).
9. Adequate renal function: creatinine clearance rate ≥ 60 ml/min or Creatinine ≤ 1.5×
upper limit of normal value.
Exclusion Criteria:
1. Patients with recurrent or metastatic nasopharyngeal carcinoma.
2. Histologically confirmed with keratinizing squamous cell carcinoma of the
nasopharynx.
3. Prior therapy with radiation or systemic chemotherapy.
4. Women in the period of pregnancy, lactation, or reproductive without effective
contraceptive measures.
5. Seropositivity for human immunodeficiency virus (HIV).
6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma
in situ of the cervix).
7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti- PD-L1,
anti-CTLA-4 antibodies.
8. Patients with immunodeficiency disease or a history of organ transplantation.
9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other
immunosuppressants within 4 weeks.
10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
11. Patients with severe, uncontrolled disease or infections.
12. Received other research drugs or in other clinical trials at the same time.
13. Refuse or fail to sign the informed consent .
14. Patients with other treatment contraindications.
15. Patients with personality or mental disorders, incapacity or limited capacity for
civil conduct.
16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV
deoxyribonucleic acid (HBV DNA) ≥1000cps/ml or 200 IU/ml.
17. Patients with positive HCV antibody test will only be enrolled in this study if the
PCR test for HCV RNA is negative.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Foshan First People's Hospital
Address:
City:
Foshan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ning Zhang
Facility:
Name:
Affiliated cancer hospital and institute of guangzhou medical university
Address:
City:
Guangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Bin Qi
Facility:
Name:
Sun Yat-Sen Memorial Hospital
Address:
City:
Guangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xingsheng Qiu
Facility:
Name:
The affiliated panyu central hospital of guangzhou medical university
Address:
City:
Guangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Guorong Zou
Facility:
Name:
ZhuJiang Hospital of Southern Medical University
Address:
City:
Guangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Junguo Bu
Facility:
Name:
Liuzhou Workers Hospital
Address:
City:
Liuzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ying Lu
Facility:
Name:
Guangxi Medical University Affiliated Cancer Hospital
Address:
City:
Nanning
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ling Li
Facility:
Name:
Cancer hospital of Shantou university medical college
Address:
City:
Shantou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Chuangzhen Chen
Facility:
Name:
Cancer hospital Chinese academy of medical sciences, Shenzhen center
Address:
City:
Shenzhen
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jianggu Zhang
Facility:
Name:
The second people's hospital of Shenzhen
Address:
City:
Shenzhen
Country:
China
Status:
Recruiting
Contact:
Last name:
Beiping Miao
Facility:
Name:
The university of Hongkong - Shenzhen hospital
Address:
City:
Shenzhen
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jishi Li
Facility:
Name:
Guangdong Medical School First Affiliated Hospital
Address:
City:
Zhangjiang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Danxian Jiang
Start date:
June 18, 2024
Completion date:
June 18, 2028
Lead sponsor:
Agency:
Sun Yat-sen University
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/NCT06455410
