Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma

November 22, 2021 updated by: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Randomized Phase II Trial of Concurrent Chemoradiotherapy With or Without Nimotuzumab for High Risk Nasopharyngeal Carcinoma After Induction Chemotherapy

This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without EGFR blocker Nimotuzumab for high risk advanced nasopharyngeal carcinoma(NPC) , determining whether concurrent chemoradiotherapy(CCRT) combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced NPC.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, although NCCN(National Comprehensive Cancer Network) guidelines recommend induction chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for locally advanced nasopharyngeal carcinoma (stage II-IVa),there is still about 20-30% of patients with locally advanced nasopharyngeal carcinoma experienced recurrence and metastasis after radical treatment.

Our previous results showed that patients with plasma Epstein-Barr virus(EBV) DNA> 0 copy/mL or stable disease/progressive disease(SD/PD) after induction chemotherapy had a significantly higher risk of disease progression than patients with plasma EBV DNA=0 copy/mL and complete response/partial response(CR/PR),according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these high-risk patients, the urgent clinical problem to be solved is whether increased treatment intensity during concurrent chemoradiotherapy can improve their survival rates.

Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal carcinoma.Multiple retrospective studies have shown that chemoradiotherapy combined with the EGFR blocker nimotuzumab improved the survival rate of patients with locally advanced nasopharyngeal carcinoma compared with chemoradiotherapy alone. However, phase II randomized clinical trial about the incorporation of nimotuzumab into concurrent chemoradiotherapy is still limited.

This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without Nimotuzumab for high risk locally advanced NPC patients, determining whether concurrent chemoradiotherapy combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced nasopharyngeal carcinoma.

Study Type

Interventional

Enrollment (Actual)

246

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen Universitty Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18-70, regardless of sex.
  2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, type of WHO II or III, clinical stage II-IVa (according to the 8th American Joint Committee on Cancer[AJCC] edition)
  3. Patients with plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy
  4. ECOG (Eastern Cooperative Oncology Group) score: 0-1
  5. Women in their reproductive years should ensure that they use contraception during the study period.
  6. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
  7. Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 2.5 times the upper limit of normal value (ULN), total bilirubin <2.0×ULN.
  8. Renal function: serum creatinine <1.5×ULN
  9. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;

Exclusion Criteria:

  1. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
  2. Receiving radiotherapy or chemotherapy or targeted therapy previously
  3. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  4. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
  5. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
  6. Severe, uncontrolled medical conditions and infections.
  7. At the same time using other test drugs or in other clinical trials.
  8. Refusal or inability to sign informed consent to participate in the trial.
  9. Other treatment contraindications.
  10. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CCRT + Nimotuzumab
Patients whose plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-fu 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) + nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
Drug: CCRT+Nimotuzumab
concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) + Nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
Other Names:
  • Nimotuzumab
ACTIVE_COMPARATOR: CCRT alone
Patients whose plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-fu 5-fu 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) )
Drug: CCRT alone
concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy )

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progress-free survival (PFS)
Time Frame: 2 years
Defined from date of randomization to date of first documentation of progression or death due to any cause
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) the last follow-up.
Time Frame: 2 years
Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.
2 years
Locoregional Relapse-Free Survival (LRFS)
Time Frame: 2 years
Defined from date of randomization to date of first documentation of locoregional relapse or the date of death from any cause or until the date of the last follow-up visit
2 years
Distant Metastasis-Free Survival (DMFS)
Time Frame: 2 years
Defined from date of randomization to date of first documentation of distant metastases or the date of death from any cause or until the date of the last follow-up visit
2 years
Objective Response Rate (ORR)
Time Frame: Three months after the completion of the CCRT with or without Nimotuzumab treatment
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)
Three months after the completion of the CCRT with or without Nimotuzumab treatment
Incidence rate of adverse events (AEs)
Time Frame: 2 years
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.
2 years
Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
Time Frame: 2 years
Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.
2 years
Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes
Time Frame: 2 years
The frequency of anti-EGFR specific T cells is evaluated centrally by means of flow cytometry
2 years
Plasma EBV DNA copy number
Time Frame: 2 years
Plasma EBV DNA copy number in both arms was assessed by Quantitative real time polymerase chain reaction(qRT-PCR) at pretreatment, after two cycle induction chemotherapy, during CCRT and follow up time . The predictive value of plasma EBV DNA copy number was assessed by survival analysis.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Haiqiang Mai, MD,PhD, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 12, 2019

Primary Completion (ANTICIPATED)

December 1, 2022

Study Completion (ANTICIPATED)

December 1, 2026

Study Registration Dates

First Submitted

January 7, 2020

First Submitted That Met QC Criteria

January 7, 2020

First Posted (ACTUAL)

January 10, 2020

Study Record Updates

Last Update Posted (ACTUAL)

December 6, 2021

Last Update Submitted That Met QC Criteria

November 22, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2019-191

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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