Radiotherapy Plus Nimotuzumab or Cisplatin in Nasopharyngeal Carcinoma

Sun Yat-sen University

Status and phase: Enrolling; Phase 3

Conditions: Nasopharyngeal Carcinoma

Treatments: Drug: RT plus Cisplatin; Drug: RT plus Nimotuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04456322

2020-FXY-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 326 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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326 participants in 2 patient groups

RT plus Nimotuzumab

Experimental group

Description:

Patients with pretreatment plasma EBV DNA\<1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy ( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)

Treatment:

Drug: RT plus Nimotuzumab

RT plus Cisplatin

Active Comparator group

Description:

Patients with pretreatment plasma EBV DNA\<1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) )

Treatment:

Drug: RT plus Cisplatin