Anti-EGFR Therapy Plus IMRT Concurrent Chemoradiotherapy in Locally Advanced NPC Resistant to Induction Chemotherapy
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): cetuximab (CTX) or nimotuzumab (NTZ)
Intervention type(s): Drug
Intervention description(s): The patients will receive IMRT combined with anti-EGFR monoclonal antibody concurrent chemoradiotherapy. The specific treatment description is included in arm description.
Intervention MeSH terms: Cetuximab; Nimotuzumab
Intervention model: Single Group Assignment
Intervention model description: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: nasopharyngeal carcinoma; IMRT; anti-EGFR monoclonal antibody; induced chemotherapy resistance