Intensified Treatments for Patients With Locally Advanced Nasopharyngeal Carcinoma With Detectable EBV DNA After One Cycle GP Regime Neoadjuvant Chemotherapy

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05772208

Collaborator

(none)

459

Enrollment

Location

Arms

Anticipated Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this multicenter randomized non-inferior study is to compare the additon of camrelizumab or nimotuzumab to neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma patients whose EBV DNA remained detectable after one cycle neoadjuvant chemotherapy using GP regimen. The main question it aims to answer is: whether the addition of carrilizumab or nituzumab improve the treatment outcomes in the relatively poor prognostic patients identified by the response of EBV DNA. Participants will be randomized to the combination of carrilizumab and standard treatment , the combination of nituzumab and standard treatment or the standard treatment alone if their EBV DNA didn't decrease to undetectable level post first cycle of neoadjuvant chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Drug: Camrelizumab Drug: Nimotuzumab Drug: neoadjuvant chemotherapy and CCRT	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

459 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized Controlled Phase III Trial of Induction Plus Concurrent Chemoradiotherapy Plus Camrelizumab or Nimotuzumab Versus Induction Plus Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma With Detectable EBV DNA After One Cycle GP Regime Neoadjuvant Chemotherapy

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: the combination of camrelizumab and standard treatment camrelizumab 200mg q3w 2 cycle combinted with the second and third cycle neoajuvant chemotherapy and camrelizumab 200mg q3w 8 cycle starting one month after concurrent chemo-radiotherapy.	Drug: Camrelizumab camrelizumab 200mg q3w Drug: neoadjuvant chemotherapy and CCRT the second and third neoajuvant chemotherapy with GP regimen (gemcitabine 1g/m2 d1，8 plus cisplatin 75mg/m2 ) concurrent chemotherapy: single cisplatin (80mg/m2) for two cycle definitive radiotherapy for primay lesion and lymph node region.
Experimental: the combination of nimotuzumab and standard treatment nimotuzumab 200mg qw combined with the second and third cycle neoajuvant chemotherapy and nimotuzumab 200mg qw used during chemo-radiotherapy.	Drug: Nimotuzumab nimotuzumab 200mg qw Drug: neoadjuvant chemotherapy and CCRT the second and third neoajuvant chemotherapy with GP regimen (gemcitabine 1g/m2 d1，8 plus cisplatin 75mg/m2 ) concurrent chemotherapy: single cisplatin (80mg/m2) for two cycle definitive radiotherapy for primay lesion and lymph node region.
Active Comparator: standard treatment the second and third neoajuvant chemotherapy with GP regimen (gemcitabine 1g/m2 d1，8 plus cisplatin 75mg/m2 ) concurrent chemotherapy: single cisplatin (80mg/m2) for two cycle definitive radiotherapy for primay lesion and lymph node region.	Drug: neoadjuvant chemotherapy and CCRT the second and third neoajuvant chemotherapy with GP regimen (gemcitabine 1g/m2 d1，8 plus cisplatin 75mg/m2 ) concurrent chemotherapy: single cisplatin (80mg/m2) for two cycle definitive radiotherapy for primay lesion and lymph node region.

Arm

Intervention/Treatment

Experimental: the combination of camrelizumab and standard treatment

camrelizumab 200mg q3w 2 cycle combinted with the second and third cycle neoajuvant chemotherapy and camrelizumab 200mg q3w 8 cycle starting one month after concurrent chemo-radiotherapy.

Drug: Camrelizumab

camrelizumab 200mg q3w

Drug: neoadjuvant chemotherapy and CCRT

the second and third neoajuvant chemotherapy with GP regimen (gemcitabine 1g/m2 d1，8 plus cisplatin 75mg/m2 ) concurrent chemotherapy: single cisplatin (80mg/m2) for two cycle definitive radiotherapy for primay lesion and lymph node region.

Experimental: the combination of nimotuzumab and standard treatment

nimotuzumab 200mg qw combined with the second and third cycle neoajuvant chemotherapy and nimotuzumab 200mg qw used during chemo-radiotherapy.

Drug: Nimotuzumab

nimotuzumab 200mg qw

Drug: neoadjuvant chemotherapy and CCRT

Active Comparator: standard treatment

Drug: neoadjuvant chemotherapy and CCRT

Outcome Measures

Primary Outcome Measures

Progression-free survival [3 years]
Defined from date of randomization to date of first documentation of progression or death due to any cause

Secondary Outcome Measures

Overall survival [3 years]
Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.
Toxicities [3 years]
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, type of WHO II or III, EGFR+.
Age 18-70 years.
Clinical stage III-IVa (based on the 8th American Joint Committee on Cancer[AJCC] edition).
Patients with detectable pre-treatment plasma EBV DNA which remained detectable after one cycle neoadjuvant.
ECOG (Eastern Cooperative Oncology Group) score: 0-1
Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 1.5 times the upper limit of normal value (ULN), total bilirubin <1.0×ULN.
Renal function: serum creatinine <1×ULN.
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.

Exclusion Criteria:

Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
Receiving radiotherapy or chemotherapy or targeted therapy previously
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
Severe, uncontrolled medical conditions and infections.
At the same time using other test drugs or in other clinical trials.
Refusal or inability to sign informed consent to participate in the trial.
Emotional disturbance or mental