Clinical trial NCT02421640: Phase II Trial of TIL Following CCRT in Patients With Locoregionally Advanced NPC
Official title: A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes and Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-04-20
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progress-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Locoregional Relapse-Free Survival (LRRF)
timeFrame: 3 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 3 years
measure: Complete Response (CR)
timeFrame: after the completion of the chemoradiotherapy treatment (up to 9 weeks)
measure: Determine the toxic effects in these patients.
timeFrame: 4 weeks
measure: Determine the molecular expression of EBV DNA.
timeFrame: 12 weeks
measure: Determine the quality of life (QoL) of these regimens in these patients.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Haiqiang Mai
state: Guangdong
Study officials:
affiliation: Cancer center
name: Haiqiang Mai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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