GC Regimen Chemotherapy Plus CIK Cells for Metastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and South Asia. After radiotherapy, some patients with nasopharyngeal carcinoma still had distant metastasis. In recent years, some chemotherapeutic agents, such as gemcitabine, cisplatin, were used to treat patients with advanced nasopharyngeal carcinoma, including those with local recurrence and distant metastases, with a certain short-term effect. However, chemotherapy alone is still not ideal for effectively improving the prognosis of patients with advanced nasopharyngeal carcinoma. Therefore, it is necessary to develop more-effective adjuvant therapies. CIK cells (cytokine induced killer cells, CIK) are a population of heterogeneous cells generated by the in vitro amplification of mononuclear cells in peripheral blood. The cells are co-induced with multiple cytokines; the lymphocytes with co-expression of CD3+CD56+ have the strongest anti-tumor effect. Because of their non-MHC restricted tumor killing activity, CIK cells have a powerful anti-tumor effect both in vitro and in vivo, which spans a broad anti-tumor spectrum. In this study, the patients with post-radiotherapy distant metastasis of NPC will be treated with autologous CIK cells in combination with Gemcitabine plus Cisplatin regimen chemotherapy(GC). The purpose of this study is to observe and evaluate the toxic side effects and the short- and long-term efficacy of CIK used in combination with GC chemotherapy to treat NPC in patients with distant metastasis after radiotherapy. Patients and Methods: 40 patients with distant metastasis after radiotherapy will accept 4 cycles chemotherapy of Gemcitabine plus cisplatin regimen and then are randomized divided into 2 groups. The 20 patients in GC+CIK group will be treated with maintaining therapy of adoptive autologous CIK cell transfusion sequentially; the other 20 patients will be followed-up only without CIK cells treatment. The safety of chemotherapy and CIK cells transfusion and the tumor regression status will be observed. The early response and long-term efficacy of two groups patients who accept GC chemotherapy or GC +CIK bio-therapy will be investigated.

Official Title
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Autologous Cytokine-Induced Killer Cell Transfusion in Combination With Gemcitabine Plus Cisplatin Regimen Chemotherapy for Metastatic Nasopharyngeal Carcinoma

Conditions
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Stage IV Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: GC chemotherapy plus CIK cells (Gemcitabine, Cisplatin, Autologous CIK cells)
* Drug: GC chemotherapy (Gemcitabine, Cisplatin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The primary lesions of all patients were classified as undifferentiated, non-keratinizing carcinoma at the initial stage for treatment (WHO, 1991 criteria) and no distant metastasis was observed based on imaging studies before radiotherapy ; all patients had received standard doses of radiotherapy, were regularly followed-up after radiotherapy, and had distant metastatic lesions revealed by imaging studies; metastases were found more than 6 months after the end of radiotherapy, with the expected survival time of more than 3 months; in each case, no more than 10 metastatic lesions were found in the imaging studies; Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1; the bone marrow functioned normally (WBC > 4.0×109/L, Hb > 120 g/L, PLT > 100×109/L); the ECG results were normal, and the liver and kidney were functional. Exclusion Criteria: Patients were excluded if they had central nervous system metastases; uncontrolled infection; underlying disease that was severe or life-threatening; the patients were pregnant or lactating; ECOG perform status ≥ 2; the patients who are suffering from auto immune diseases or patients who need to accept glucocorticoid treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: GC chemotherapy plus CIK cells<br>A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks); however,the other 20 patients will not accept CIK cells treatment. After the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus 8 cycles CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated. | Drug: GC chemotherapy plus CIK cells (Gemcitabine, Cisplatin, Autologous CIK cells)<br>* A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks);the other 20 patients will not accept CIK cells treatment. Afer the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated.<br>* Other names: Autologous CIK cells;|
| Active Comparator: GC chemotherapy<br>A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks);the other 20 patients will not accept CIK cells treatment. After the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated. | Drug: GC chemotherapy (Gemcitabine, Cisplatin)<br>* A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks);the other 20 patients will not accept CIK cells treatment. Afer the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated.<br>* Other names: Gemcitabine (Zefei) and Cisplatin (Nuoxin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) | (According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months. | 
| Partial remission (PR) | (According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months. | 
| Stable disease (SD) | (According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months. | 
| Progressive disease (PD) | (According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival time (OS) | OS is defined as the time from randomization until death from any cause; TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths; PFS is defined as the time from randomization until objective tumor progression or death. | Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment. | 
| time to progression (TTP) | OS is defined as the time from randomization until death from any cause; TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths; PFS is defined as the time from randomization until objective tumor progression or death. | Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment. | 
| progression free survival(PFS) | OS is defined as the time from randomization until death from any cause; TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths; PFS is defined as the time from randomization until objective tumor progression or death. | Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasopharyngeal carcinoma, metastasis, gemcitabine, CIK cells