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Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma

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ClinicalTrials.gov Identifier: NCT04223024
Recruitment Status : Active, not recruiting
First Posted : January 10, 2020
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Nasopharyngeal Carcinoma Drug: CCRT+Nimotuzumab Drug: CCRT alone Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 246 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Randomized Phase II Trial of Concurrent Chemoradiotherapy With or Without Nimotuzumab for High Risk Nasopharyngeal Carcinoma After Induction Chemotherapy
Actual Study Start Date : December 12, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


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 Name: 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 )




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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. 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

  3. 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

  4. 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)

  5. 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.

  6. 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.

  7. 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

  8. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04223024


Locations
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China, Guangdong
Sun Yat-sen Universitty Cancer Center
Guangzhou, Guangdong, China, 510060
Sponsors and Collaborators
Sun Yat-sen University
Investigators
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Principal Investigator: Haiqiang Mai, MD,PhD Sun Yat-sen University
Publications:

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Responsible Party: Hai-Qiang Mai,MD,PhD, Deputy Director of the Department of Nasopharyngeal Carcinoma, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04223024    
Other Study ID Numbers: B2019-191
First Posted: January 10, 2020    Key Record Dates
Last Update Posted: December 6, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Nasopharyngeal Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Nimotuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents