Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Docetaxel

Nimotuzumab

Cetuximab

Fluorouracil

Cisplatin

Immunoglobulins

Immunologic Factors

In the induction chemotherapy phase, TP regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3, repeat every 3 weeks) or TPF regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3+5-FU 750mg/m2, CIV, 120h, 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.

The patients will receive IMRT combined with anti-EGFR monoclonal antibody concurrent chemoradiotherapy in locally advanced oropharyngeal carcinoma with induced chemotherapy resistance. The specific treatment description is included in arm description.

Anti-EGFR monoclonal antibody

Xiaoshen Wang, MD, Ph.D

Xiaoshuang Niu, MD

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 oropharyngeal carcinoma (OPC) with induced chemotherapy resistance.

Eligibility criteria include histologically confirmed locally advanced OPC 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. Prior induction chemotherapy with platinum was allowed.

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.

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 oropharyngeal carcinoma (OPC) with induced chemotherapy resistance.

Eligibility criteria include histologically confirmed locally advanced OPC with induced chemotherapy resistance 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). Prior induction chemotherapy with platinum was allowed.

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 TPF regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3+5-FU 750mg/m2, CIV, 120h, 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 oropharyngeal 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.

Anti-EGFR Therapy With IMRT Concurrent Chemoradiotherapy in Locally Advanced OPC Resistant to Induction Chemotherapy

IMRT Combined With Concurrent Chemotherapy and Anti-EGFR Monoclonal Antibody in Locally Advanced Oropharyngeal Carcinoma Resistant to Induction Chemotherapy: a Multicenter Prospective Phase II Study.

PFS is calculated from the date of the enrollment to the date of disease progression or the date of death for any cause.

Fudan University

Professor

Rare Diseases

Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms

Nasopharyngeal Diseases

Gemcitabine

Capecitabine

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Two cycles of TP (docetaxel+cisplatin), TPF(docetaxel+cisplatin+5-FU), TPX (docetaxel+cisplatin+capecitabine) or GP regimen (gemcitabine+cisplatin) followed by radiotherapy (66-70.4Gy) combined with PD-1 inhibitor (every 3 weeks) and anti-EGFR monoclonal antibody (every 1 week) when responses to induction chemotherapy are less than 50% Partial Response (PR) or EBVDNA copy number decreased by less than 50%.

Drug: PD-1 inhibitor and anti-EGFR monoclonal antibody The patients will receive radiotherapy (66-70.4Gy) combined with PD-1 inhibitor (every 3 weeks) and anti-EGFR monoclonal antibody (every 1 week). The specific treatment description is included in arm description.

Anti-EGFR and PD-1 inhibitor arm

Ruichen Li, MD

Xiaoshen Wang

Because nasopharyngeal carcinoma （NPC）is very sensitive to radiation and the specificity of the anatomical structure, radiotherapy has become the core treatment for NPC. Although induction chemotherapy combined with cisplatin-based concurrent chemoradiotherapy can effectively improve the overall survival and progression-free survival of NPC, such a sequential pattern can further exacerbate the toxic side effects of treatment, such as mucosal reactions and gastrointestinal toxicity. Therefore, it is particularly important to explore another treatment mode with high efficiency and low toxicity. Secondly, patients with poor response after induction chemotherapy indicate chemotherapy resistance. Whether patients can still benefit from concurrent platinum-based chemotherapy in the followed radiotherapy is doubtful. PD-1 inhibitor and anti-EGFR monoclonal antibody have proved to improve outcomes of head and neck cancers including EBV-related NPC, which have also showed relatively low toxicity. In this study, radiotherapy combined with PD-1 inhibitor and anti-EGFR monoclonal antibody were applied to treat patients with locally advanced NPC who were resistant to induction chemotherapy.

PD-1 Inhibitor Plus Anti-EGFR Therapy And Radiotherapy in Locally Advanced NPC Resistant to Induction Chemotherapy

Radiotherapy Combined With PD-1 Inhibitor and Anti-EGFR Monoclonal Antibody for Locally Advanced Nasopharyngeal Carcinoma Resistant to Induction Chemotherapy: A Prospective Phase II Study

The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anti-EGFR Therapy With IMRT Concurrent Chemoradiotherapy in Locally Advanced OPC Resistant to Induction Chemotherapy	NCT04508829	Oropharyngeal C...	Anti-EGFR monoc...	18 Years - 70 Years	Fudan University
PD-1 Inhibitor Plus Anti-EGFR Therapy And Radiotherapy in Locally Advanced NPC Resistant to Induction Chemotherapy	NCT06156878	Nasopharyngeal ...	Anti-EGFR and P...	18 Years - 75 Years	Fudan University
Anti-EGFR Therapy With IMRT Concurrent Chemoradiotherapy in Locally Advanced OPC Resistant to Induction Chemotherapy	NCT04508829	Oropharyngeal C...	Anti-EGFR monoc...	18 Years - 70 Years	Fudan University

Spots Global Cancer Trial Database for induced chemotherapy resistance