Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
B2019-191
- NCT ID:
NCT04223024
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| CCRT+Nimotuzumab | Nimotuzumab | CCRT + Nimotuzumab |
| CCRT alone | | CCRT alone |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| CCRT + Nimotuzumab | Experimental | 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) | |
| CCRT alone | Active Comparator | 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) ) | |
Eligibility 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.
| Maximum Eligible Age: | 70 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progress-free survival (PFS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Defined from date of randomization to date of first documentation of progression or death due to any cause |
Secondary Outcome Measures
| Measure: | Overall Survival (OS) the last follow-up. |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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. |
| Measure: | Locoregional Relapse-Free Survival (LRFS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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 |
| Measure: | Distant Metastasis-Free Survival (DMFS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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 |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Three months after the completion of the CCRT with or without Nimotuzumab treatment |
| Safety Issue: | |
| 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) |
| Measure: | Incidence rate of adverse events (AEs) |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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. |
| Measure: | Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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. |
| Measure: | Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | The frequency of anti-EGFR specific T cells is evaluated centrally by means of flow cytometry |
| Measure: | Change of QoL |
| Time Frame: | 1 years |
| Safety Issue: | |
| Description: | QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy |
| Measure: | Change of EORTC quality of life questionnaire(QLQ) Head and Neck score |
| Time Frame: | 1 years |
| Safety Issue: | |
| Description: | QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.All of the scores mentioned above were assessed at the below time point:before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy |
| Measure: | Plasma EBV DNA copy number |
| Time Frame: | 2 years |
| Safety Issue: | |
| 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Sun Yat-sen University |
Last Updated
April 15, 2020
