Clinical trial NCT04223024: Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma
Official title: Randomized Phase II Trial of Concurrent Chemoradiotherapy With or Without Nimotuzumab for High Risk Nasopharyngeal Carcinoma After Induction Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-01-10
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without EGFR blocker Nimotuzumab for high risk advanced nasopharyngeal carcinoma(NPC) , determining whether concurrent chemoradiotherapy(CCRT) combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced NPC.

Detailed description: Currently, although NCCN(National Comprehensive Cancer Network) guidelines recommend induction chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for locally advanced nasopharyngeal carcinoma (stage II-IVa),there is still about 20-30% of patients with locally advanced nasopharyngeal carcinoma experienced recurrence and metastasis after radical treatment.

Our previous results showed that patients with plasma Epstein-Barr virus(EBV) DNA\> 0 copy/mL or stable disease/progressive disease(SD/PD) after induction chemotherapy had a significantly higher risk of disease progression than patients with plasma EBV DNA=0 copy/mL and complete response/partial response(CR/PR),according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these high-risk patients, the urgent clinical problem to be solved is whether increased treatment intensity during concurrent chemoradiotherapy can improve their survival rates.

Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal carcinoma.Multiple retrospective studies have shown that chemoradiotherapy combined with the EGFR blocker nimotuzumab improved the survival rate of patients with locally advanced nasopharyngeal carcinoma compared with chemoradiotherapy alone. However, phase II randomized clinical trial about the incorporation of nimotuzumab into concurrent chemoradiotherapy is still limited.

This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without Nimotuzumab for high risk locally advanced NPC patients, determining whether concurrent chemoradiotherapy combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced nasopharyngeal carcinoma.

Eligibility criteria: Inclusion Criteria:

1. Age 18-70, regardless of sex.
2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma with positive EGFR expression, type of WHO II or III, clinical stage II-IVa (according to the 8th American Joint Committee on Cancer\[AJCC\] edition)
3. Patients with plasma EBV DNA\> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy
4. ECOG (Eastern Cooperative Oncology Group) score: 0-1
5. Women in their reproductive years should ensure that they use contraception during the study period.
6. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
7. Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)\< 2.5 times the upper limit of normal value (ULN), total bilirubin \<2.0×ULN.
8. Renal function: serum creatinine \<1.5×ULN
9. 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:

1. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
2. Receiving radiotherapy or chemotherapy or targeted therapy previously
3. 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.
4. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
5. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
6. Severe, uncontrolled medical conditions and infections.
7. At the same time using other test drugs or in other clinical trials.
8. Refusal or inability to sign informed consent to participate in the trial.
9. Other treatment contraindications.
10. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.

Primary outcomes:
measure: Progress-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS) the last follow-up.
timeFrame: 2 years
measure: Locoregional Relapse-Free Survival (LRFS)
timeFrame: 2 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 2 years
measure: Objective Response Rate (ORR)
timeFrame: Three months after the completion of the CCRT with or without Nimotuzumab treatment
measure: Incidence rate of adverse events (AEs)
timeFrame: 2 years
measure: Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
timeFrame: 2 years
measure: Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes
timeFrame: 2 years
measure: Plasma EBV DNA copy number
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Universitty Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Haiqiang Mai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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