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

NCT ID: NCT04508829

Last Updated: 2022-04-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-01
• Study Completion Date: 2023-12-01

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 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.

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 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.

Conditions

Oropharyngeal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anti-EGFR arm

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.

Group Type: EXPERIMENTAL

Anti-EGFR monoclonal antibody

Intervention Type: DRUG

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.

Interventions

Anti-EGFR monoclonal antibody

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed locally advanced OPC with Induced chemotherapy resistance;
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xiaoshen Wang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaoshen Wang, MD, Ph.D

Role: CONTACT

ruijin702@163.com

+8618017312704

Facility Contacts

Xiaoshen Wang, MD, Ph.D

Role: primary

ruijin702@163.com

+8618017312704

Xiaoshuang Niu, MD

Role: backup

xniu13@fudan.edu.cn

+8618121299548

Other Identifiers

OPC-anti-EGFR-01

Identifier Type: -

Identifier Source: org_study_id