Clinical trial NCT04508816: Anti-EGFR Therapy Plus IMRT Concurrent Chemoradiotherapy in Locally Advanced NPC Resistant to Induction Chemotherapy
Official title: IMRT Combined With Concurrent Chemotherapy and Anti-EGFR Monoclonal Antibody for Locally Advanced Nasopharyngeal Carcinoma Resistant to Induction Chemotherapy: a Multicenter Prospective Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: nasopharyngeal carcinoma
IMRT
anti-EGFR monoclonal antibody
induced chemotherapy resistance
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-08-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced nasopharyngeal carcinoma with induced chemotherapy resistance.

Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count, normal hepatic function and normal renal function.

Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.

The full-set pretreatment evaluation will be performed to every patient. All patients in this study will receive intensity-modulated radiation therapy (IMRT). The primary endpoints of this study is progression-free survival (PFS) and adverse events (AE) rate.

Detailed description: This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced nasopharyngeal carcinoma with induced chemotherapy resistance.

Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count (white blood cell counts ≥4×1012/L, hemoglobin level ≥100g/L and platelet counts ≥100×1012/L), normal hepatic function (total bilirubin level ≤1.5 mg/dl, alanine aminotransferase and aspartate aminotransferase levels ≤1.5 times the upper limit of normal) and normal renal function (creatinine ≤ 1.5 times the upper limit of normal).

Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.

The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT).

In the induction chemotherapy phase, TP regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3, repeat every 3 weeks) or GP regimen (Gemcitabine 1.0g/m2, D1, 8 + DDP 25mg/m2 , D1-3, repeat every 3 weeks) will be used. Cetuximab 400mg/m2 will be used one week before radiotherapy and 250mg/m2/week during IMRT, or nimotuzumab 200mg/week; meanwhile, cisplatin 80mg/m2 will be used every 3 weeks.

Adverse events (AEs) will be evaluated every week during CCRT based on the evaluation criteria of adverse reactions of CTCAE V4.0. Tumor response is assessed at the end of CCRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Radiation-related acute and late toxicities are graded according to the Radiation Therapy Oncology Group (RTOG). Late toxicities are evaluated beyond three months from the end of radiotherapy.

After the completion of CCRT, all patients will be followed up every 3 months during the first years, every 6 months for the following 2-5 years, and annually thereafter. Local recurrence is confirmed by nasopharynx MRI or histological biopsy. Regional recurrence is confirmed by fine needle aspiration or surgical biopsy. Distant metastases is detected by imaging examinations including PETCT, bone Emission Computed Tomography (ECT), CT, MRI or confirmed by histological confirmation of biopsy.

The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS). PFS is calculated from the date of enrollment to the date of disease progression or the date of death for any cause.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed locally advanced NPC;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
* Normal complete blood count;
* Normal hepatic function;
* Normal renal function (creatinine ≤ 1.5 times the upper limit of normal).

Exclusion Criteria:

* Previous radiotherapy;
* A history of any other type of malignancy;
* Pregnancy or lactation;
* Allergy to anti-EGFR monoclonal antibody;
* Obvious disfunction of liver, renal, cardiac or lung function;
* Un controlled infection;
* Systemic metastasis or distant metastasis;
* Patients with severe gastrointestinal diseases;
* Patients with mental disorders affecting patient participation in trial judgement.

Primary outcomes:
measure: PFS
timeFrame: 3-year PFS
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xiaoshen Wang
Study officials:
affiliation: Fudan University
name: Xiaoshen Wang, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: