Clinical trial NCT04456322: Radiotherapy Plus Nimotuzumab or Cisplatin in Nasopharyngeal Carcinoma
Official title: A Randomized Non-inferiority Trial of Radiotherapy Plus Nimotuzumab or Cisplatin in Patients With Favorable Response to Induction Chemotherapy for Low-risk Locoregionally Advanced-Staged Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-07-02
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker nimotuzumab versus radiotherapy plus cisplatin(CCRT) for nasopharyngeal carcinoma (NPC) patients with favorable response to induction chemotheray(IC), determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT and may provide new evidence for individualized comprehensive treatment of locoregionally advanced NPC.

Detailed description: Currently, 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). However, although induction chemotherapy combined with cisplatin based concurrent radiotherapy (CCRT) can significantly improve the survival of patients, the side effects during radiotherapy are more serious.

Previous studies have demonstrated that with a cut-off point of 1500 copies/mL, NPC patients could be segregated into a low-risk subgroup and a high-risk subgroup. Besides, our previous results showed that patients with plasma Epstein-Barr virus (EBV) DNA= 0 copy/mL and complete response/partial response (CR/PR) after induction chemotherapy had a significantly lower risk of disease progression than patients with plasma EBV DNA\>0 copy/mL and stable disease /progressive disease (SD/PD),according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these low-risk and chemotheray sensitive patients, it can be considered to reduce the current standard treatment intensity without affecting the survival rate of patients, which reduces the side effects of patients and improve the their life qualities.

Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal carcinoma. A retrospective study suggested that there was no significant difference in the 3-year overall survival between NPC patients who received nimotuzumab / cetuximab plus radiotherapy and those who received standard CCRT. Besides, in terms of hepatorenal toxicity, anti-EGFR drugs showed better safety compared with traditional cisplatin chemotherapy. Up to now, randomized clinical trial about the application of nimotuzumab after IC is still limited.

This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker nimotuzumab versus radiotherapy plus cisplatin for NPC patients with favorable response after IC, determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT after IC and may provide new evidence for individualized comprehensive treatment of locoregionally advanced NPC.

Eligibility criteria: Inclusion Criteria:

1. Age 18-70, regardless of sex.
2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, type of WHO II or III, clinical stage II-IVa (except N3)(according to the 8th American Joint Committee on Cancer\[AJCC\] edition)
3. Patients with pre-treatment plasma EBV DNA\<1500 copies/mL
4. Patients with plasma EBV DNA= 0 copy/mL and CR/PR according to RECIST after two cycle induction chemotherapy
5. ECOG (Eastern Cooperative Oncology Group) score: 0-1
6. Women in their reproductive years should ensure that they use contraception during the study period.
7. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
8. Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)\< 2.5 times the upper limit of normal value (ULN), total bilirubin \<2.0×ULN.
9. Renal function: serum creatinine \<1.5×ULN
10. 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: Progression-Free Survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS)
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: Change of QoL
timeFrame: 1 years
measure: Change of EORTC quality of life questionnaire(QLQ) Head and Neck score
timeFrame: 1 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:
References:
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