Phase II Trial of TIL Following CCRT in Patients With Locoregionally Advanced NPC

Study Overview
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Brief Summary
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This is a Phase II trial to study the effectiveness and security of cisplatin concurrent chemoradiotherapy plus TIL versus cisplatin concurrent chemoradiotherapy only with IMRT in treating patients with locoregionally advanced high risk nasopharyngeal carcinoma.

Detailed Description
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Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. For locoregionally advanced NPC,especially for the high risk NPC (EB virus DNA ≥ 4000 copies/ml) ,the incidence of treatment failure is still high. Although concurrent chemoradiotherapy (CCRT) can improve the treatment outcomes of these patients, approximately 25% of locoregionally advanced NPCs relapse. Adjuvant chemotherapy or inducing chemotherapy addition to CCRT did not significantly improve patient survival compared to CCRT alone. Hence, there is an urgent need for novel therapies to improve disease-free survival and reduce treatment-related toxicity in patients. Accumulating evidence shows that tumor-infiltrating lymphocytes (TILs) selected for tumor recognition and greatly expanded in vitro are especially effective for treating cancer patients.The investigations phase I results showed that TILs following CCRT as a novel treatment strategy in locoregionally advanced NPC patients resulted in sustained anti-tumor activity and anti-EBV immune responses, associated with a good tolerance. This is a Phase II trial to study the effectiveness and security of cisplatin CCRT plus TIL versus cisplatin CCRT only with IMRT in treating patients with locoregionally advanced high risk NPC.

Official Title
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A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes and Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Cisplatin+TIL
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III Original clinical staged as T3-4N1-3 M0 or any T、N2-3M0（according to the 7th AJCC edition） No evidence of distant metastasis (M0) Plasm EB Virus DNA≥4000copies/ml Male and no pregnant female Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1 WBC ≥ 4×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 2.0×ULN) With normal renal function test (Creatinine ≤ 1.5×ULN) Exclusion Criteria: Patients have evidence of relapse or distant metastasis Histologically confirmed keratinizing squamous cell carcinoma (WHO I) Receiving radiotherapy or chemotherapy previously The presence of uncontrolled life-threatening illness 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. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). Concurrent systemic steroid therapy HIV positive Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin+TIL<br>Cisplatin concurrent chemoradiotherapy(CCRT) combined with tumor-infiltrating lymphocyte (TIL) | Drug: Cisplatin+TIL<br>* cisplatin 100mg/m2(every three weeks),D1,D22,D43 of radiotherapy,then TIL infusing following concurrent chemoradiotherapy<br>* Other names: DDP;|
| Active Comparator: Cisplatin<br>Cisplatin concurrent chemoradiotherapy(CCRT) only | Drug: Cisplatin<br>* cisplatin 100mg/m2(every three weeks),D1,D22,D43 of radiotherapy only<br>* Other names: DDP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival | Progress-free survival is calculated from the date of randomization to the date of the first progress at any site. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up. | 3 years | 
| Locoregional Relapse-Free Survival (LRRF) | The LRRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit. | 3 years | 
| Distant Metastasis-Free Survival (DMFS) | The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit. | 3 years | 
| Complete Response (CR) | CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the chemoradiotherapy treatment. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only. | after the completion of the chemoradiotherapy treatment (up to 9 weeks) | 
| Determine the toxic effects in these patients. | Patients will be monitored for clinical toxicity by standard NIH criteria. A time period of 4 weeks will constitute the time for clinical safety monitoring. | 4 weeks | 
| Determine the molecular expression of EBV DNA. | The molecular expression responses of the patients, including their plasma EBV DNA load, IFN levels and the expansion of EBV-antigen specific T cells. | 12 weeks | 
| Determine the quality of life (QoL) of these regimens in these patients. | Administration and Monitoring Patients will be evaluated in the clinic and eligibility and informed consent obtained. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) and EORTC QLQ Head and Neck. | 4 weeks |