GC Regimen Chemotherapy Plus CIK Cells for Metastatic Nasopharyngeal Carcinoma

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

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.

Study Overview

• Status: Unknown
• Conditions: Stage IV Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: GC chemotherapy plus CIK cells (Gemcitabine, Cisplatin, Autologous CIK cells); Drug: GC chemotherapy (Gemcitabine, Cisplatin)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou city, Guangdong, China, 510080
      • Recruiting
      • Cancer Center, Sun Yat-sen University
      • Contact: Jian-jun Li, M.D. Ph.D; Phone Number: 86-2087343381; Email: lijj@sysucc.org.cn
      • Principal Investigator: Jian-jun Li, M.D. Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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 ;
2. all patients had received standard doses of radiotherapy, were regularly followed-up after radiotherapy, and had distant metastatic lesions revealed by imaging studies;
3. metastases were found more than 6 months after the end of radiotherapy, with the expected survival time of more than 3 months;
4. in each case, no more than 10 metastatic lesions were found in the imaging studies;
5. Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1;
6. the bone marrow functioned normally (WBC > 4.0×109/L, Hb > 120 g/L, PLT > 100×109/L);
7. the ECG results were normal, and the liver and kidney were functional.

Exclusion Criteria:

1. Patients were excluded if they had central nervous system metastases;
2. uncontrolled infection; underlying disease that was severe or life-threatening;
3. the patients were pregnant or lactating;
4. ECOG perform status ≥ 2;
5. the patients who are suffering from auto immune diseases or patients who need to accept glucocorticoid treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GC chemotherapy plus CIK cells; 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); 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.; Other Names: Gemcitabine (Zefei) and Cisplatin(Nuoxin) ;; Autologous CIK cells
Active Comparator: GC chemotherapy; 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); 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.; Other Names: Gemcitabine (Zefei) and Cisplatin (Nuoxin)

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jian-jun Li, M.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Anticipated): July 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: July 26, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 2, 2012

Study Record Updates

• Last Update Posted (Estimate): August 2, 2012
• Last Update Submitted That Met QC Criteria: August 1, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: gemcitabine; metastasis; nasopharyngeal carcinoma; CIK cells
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: 20120704