Study of Tumor Infiltrating Lymphocytes Following CCRT in the Treatment of Patients With Cervical Carcinoma

Study Overview
=================
Brief Summary
-----------------
A Phase I trial to evaluate the feasibility, toxicity and effectiveness of cisplatin concurrent chemoradiotherapy plus TIL in treating patients with FIGO stage IIIA to IVA cervical carcinoma.

Detailed Description
-----------------
Concurrent chemoradiotherapy (CCRT) was the standard treatment for locoregionally advanced cervical cancer, while the incidence of treatment failure is still high. Adjuvant chemotherapy or inducing chemotherapy addition to CCRT did not significantly improve patient survival compared to CCRT alone. Hence, there is a need for novel therapies to improve survival for these patients. Accumulating evidence shows that tumor-infiltrating lymphocytes (TILs) selected for tumor recognition and greatly expanded in vitro are effective for treating cervical cancer patients. This is a phase I trial to evaluate the feasibility, toxicity and effectiveness of cisplatin concurrent chemoradiotherapy plus TIL in treating patients with FIGO stage IIIA to IVA cervical carcinoma.

Official Title
-----------------
Study of Tumor Infiltrating Lymphocytes Following Concurrent Chemoradiotherapy in the Treatment of Patients With Cervical Carcinoma

Conditions
-----------------
Cervical Carcinoma

Intervention / Treatment
-----------------
* Drug: CCRT+TIL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically proven squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervical uteri Patients with stage IIIA-IVA cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) Patients who were ≥ 18 and ≤ 70 years old Patients with an ECOG performance status of 0, 1, or 2 Adequate hematological, renal, and hepatic functions defined as: granulocytes ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, total bilirubin, ALT and AST ≤ 1.5 x upper normal limit, creatinine ≤ upper normal limit Patients provided written, voluntary informed consent Patients who were accessible to follow up and management in the treatment center Exclusion Criteria: Patients with past or current history of malignancy other than the entry diagnosis except for a cured malignancy more than five years prior to enrollment Patients who received previous chemotherapy or radiotherapy Patients with active angina or documented myocardial infarction within the 6 months preceding registration and patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure, as well as a history of 2nd or 3rd degree heart blocks Patients with an active infection or other serious underlying medical conditions that would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing platinum Patients with dementia or altered mental status that would prohibit the understanding and providing of informed consent Patients with inadequate caloric and/or fluid intake

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCRT+TIL<br>Cisplatin based concurrent chemoradiotherapy(CCRT) combined with tumor-infiltrating lymphocyte (TIL) | Drug: CCRT+TIL<br>* Cisplatin based chemotherapy concurrently with radiotherapy, then TIL infusing following concurrent chemoradiotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity Evaluation | Patients will be monitored for clinical toxicity by by the National Cancer Institute Common Terminology Criteria for Adverse Events. | From chemo-radiotherapy start until Day30 after TIL infusion | 
| Feasibility of CCRT in combination with TIL successful infusion | Number of patients receiving a complete TIL infusion | 30 days after start of TIL-ACT infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Disease response evaluated after the completion of the chemoradiotherapy and TIL treatment. Achievement of complete response, partial response. | 1, 3, 6, 9, 12 months | 
| Disease control rate (DCR) | Disease response evaluated after the completion of the chemoradiotherapy and TIL treatment. Achievement of complete response, partial response or stable disease. | 1, 3, 6, 9, 12 months | 
| Disease control time (DCT) | Duration from complete response, partial response or stable disease to progression. | 1, 3, 6, 9, 12 months | 
| Immunological correlates to tumor response | Post-hoc exploratory analyses for immunological correlates to tumor response. | 1, 3, 6, 9, 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tumor Infiltrating Lymphocytes, Concurrent chemotherapy