Back to resultsConcurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma
Primary Purpose
Nasopharyngeal Carcinoma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CCRT+Nimotuzumab
CCRT alone
Sponsored by
About this trial
This is an interventional prevention trial for Nasopharyngeal Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Age 18-70, regardless of sex.
- 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)
- Patients with plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy
- ECOG (Eastern Cooperative Oncology Group) score: 0-1
- Women in their reproductive years should ensure that they use contraception during the study period.
- Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
- Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 2.5 times the upper limit of normal value (ULN), total bilirubin <2.0×ULN.
- Renal function: serum creatinine <1.5×ULN
- 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:
- Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
- Receiving radiotherapy or chemotherapy or targeted therapy previously
- 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.
- Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
- Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
- Severe, uncontrolled medical conditions and infections.
- At the same time using other test drugs or in other clinical trials.
- Refusal or inability to sign informed consent to participate in the trial.
- Other treatment contraindications.
- Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.
Sites / Locations
- Sun Yat-sen Universitty Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CCRT + Nimotuzumab
CCRT alone
Arm Description
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)
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) )
Outcomes
Primary Outcome Measures
Progress-free survival (PFS)
Defined from date of randomization to date of first documentation of progression or death due to any cause
Secondary Outcome Measures
Overall Survival (OS) the last follow-up.
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.
Locoregional Relapse-Free Survival (LRFS)
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
Distant Metastasis-Free Survival (DMFS)
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
Objective Response Rate (ORR)
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)
Incidence rate of adverse events (AEs)
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.
Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.
Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes
The frequency of anti-EGFR specific T cells is evaluated centrally by means of flow cytometry
Plasma EBV DNA copy number
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.
Full Information
NCT ID
NCT04223024
First Posted
January 7, 2020
Last Updated
November 22, 2021
Sponsor
Sun Yat-sen University
1. Study Identification
Unique Protocol Identification Number
NCT04223024
Brief Title
Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma
Official Title
Randomized Phase II Trial of Concurrent Chemoradiotherapy With or Without Nimotuzumab for High Risk Nasopharyngeal Carcinoma After Induction Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 12, 2019 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
246 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CCRT + Nimotuzumab
Arm Type
Experimental
Arm Description
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)
Arm Title
CCRT alone
Arm Type
Active Comparator
Arm Description
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) )
Intervention Type
Drug
Intervention Name(s)
CCRT+Nimotuzumab
Other Intervention Name(s)
Nimotuzumab
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
CCRT alone
Intervention Description
concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy )
Primary Outcome Measure Information:
Title
Progress-free survival (PFS)
Description
Defined from date of randomization to date of first documentation of progression or death due to any cause
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Survival (OS) the last follow-up.
Description
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.
Time Frame
2 years
Title
Locoregional Relapse-Free Survival (LRFS)
Description
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
Time Frame
2 years
Title
Distant Metastasis-Free Survival (DMFS)
Description
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
Time Frame
2 years
Title
Objective Response Rate (ORR)
Description
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)
Time Frame
Three months after the completion of the CCRT with or without Nimotuzumab treatment
Title
Incidence rate of adverse events (AEs)
Description
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.
Time Frame
2 years
Title
Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
Description
Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.
Time Frame
2 years
Title
Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes
Description
The frequency of anti-EGFR specific T cells is evaluated centrally by means of flow cytometry
Time Frame
2 years
Title
Plasma EBV DNA copy number
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-70, regardless of sex.
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)
Patients with plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy
ECOG (Eastern Cooperative Oncology Group) score: 0-1
Women in their reproductive years should ensure that they use contraception during the study period.
Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 2.5 times the upper limit of normal value (ULN), total bilirubin <2.0×ULN.
Renal function: serum creatinine <1.5×ULN
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:
Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
Receiving radiotherapy or chemotherapy or targeted therapy previously
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.
Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
Severe, uncontrolled medical conditions and infections.
At the same time using other test drugs or in other clinical trials.
Refusal or inability to sign informed consent to participate in the trial.
Other treatment contraindications.
Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiqiang Mai, MD,PhD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen Universitty Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
12. IPD Sharing Statement
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Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma
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