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

Primary Purpose

Nasopharyngeal Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Cisplatin+TIL
Cisplatin
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Haiqiang MaiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cisplatin+TIL

Cisplatin

Arm Description

Cisplatin concurrent chemoradiotherapy(CCRT) combined with tumor-infiltrating lymphocyte (TIL)

Cisplatin concurrent chemoradiotherapy(CCRT) only

Outcomes

Primary Outcome Measures

Progress-free survival
Progress-free survival is calculated from the date of randomization to the date of the first progress at any site.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 11, 2015
Last Updated
October 17, 2016
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02421640
Brief Title
Phase II Trial of TIL Following CCRT in Patients With Locoregionally Advanced NPC
Acronym
TIL
Official Title
A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes and Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2017 (Anticipated)
Study Completion Date
March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

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
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
116 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cisplatin+TIL
Arm Type
Experimental
Arm Description
Cisplatin concurrent chemoradiotherapy(CCRT) combined with tumor-infiltrating lymphocyte (TIL)
Arm Title
Cisplatin
Arm Type
Active Comparator
Arm Description
Cisplatin concurrent chemoradiotherapy(CCRT) only
Intervention Type
Drug
Intervention Name(s)
Cisplatin+TIL
Other Intervention Name(s)
DDP
Intervention Description
cisplatin 100mg/m2(every three weeks),D1,D22,D43 of radiotherapy,then TIL infusing following concurrent chemoradiotherapy
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
DDP
Intervention Description
cisplatin 100mg/m2(every three weeks),D1,D22,D43 of radiotherapy only
Primary Outcome Measure Information:
Title
Progress-free survival
Description
Progress-free survival is calculated from the date of randomization to the date of the first progress at any site.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
3 years
Title
Locoregional Relapse-Free Survival (LRRF)
Description
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.
Time Frame
3 years
Title
Distant Metastasis-Free Survival (DMFS)
Description
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.
Time Frame
3 years
Title
Complete Response (CR)
Description
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.
Time Frame
after the completion of the chemoradiotherapy treatment (up to 9 weeks)
Title
Determine the toxic effects in these patients.
Description
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.
Time Frame
4 weeks
Title
Determine the molecular expression of EBV DNA.
Description
The molecular expression responses of the patients, including their plasma EBV DNA load, IFN levels and the expansion of EBV-antigen specific T cells.
Time Frame
12 weeks
Title
Determine the quality of life (QoL) of these regimens in these patients.
Description
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.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiuyan Chen, MD,PhD
Phone
86-20-87343380
Email
chenqy@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiqiang Mai, MD,PhD
Organizational Affiliation
Cancer center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haiqiang Mai
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qiuyan Chen, MD,PhD
Phone
86-20-87343380
Email
chenqy@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
decided by the results
Citations:
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15812080
Citation
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Phase II Trial of TIL Following CCRT in Patients With Locoregionally Advanced NPC

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