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

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06156878

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Combination Product: Anti-EGFR and PD-1 inhibitor arm	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single Group AssignmentSingle Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti-EGFR and PD-1 inhibitor arm 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%.	Combination Product: Anti-EGFR and PD-1 inhibitor arm 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.

Arm

Intervention/Treatment

Experimental: Anti-EGFR and PD-1 inhibitor arm

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%.

Combination Product: Anti-EGFR and PD-1 inhibitor arm

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.

Outcome Measures

Primary Outcome Measures

PFS [3 years]
Progression Free Survival
OS [3 years]
Overall Survival

Secondary Outcome Measures

DCR [3 years]
Disease-free survival
Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG [3 years]
The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed locally advanced NPC; IHC EGFR positive; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Imaging assessment of MR after induction chemotherapy revealed the responses to induction chemotherapy are less than 50% Partial Response(PR) or EBVDNA copy number decreased by less than 50%; No prior anti-tumor treatment; 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; IHC EGFR negative; Allergy to PD-1 inhibitor; 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; Cannot take contrast-MRI imaging.