A Multi-center, Randomized, Double-blind, Phase III Clinical Trial of Leucogen Versus Placebo on Leukocyte and Platelet Whole-course Management Assisted by PFLL Chemotherapy in the Treatment of Stage IV, Recurrent or Metastatic NPC

Study Overview
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Brief Summary
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Toxic and side effects during and after chemoradiotherapy for nasopharyngeal carcinoma seriously affect patients' treatment compliance and long-term quality of life. Active and effective prediction, prevention and management of toxic and side effects is an important element to improve the prognosis of patients. Leucogen has the ability to promote the growth and maturation of granulocytes in the bone marrow and the proliferation of leukocytes, and is widely used in radiation therapy and chemotherapy-induced leukopenia in malignant carcinomas. In addition, leucogen may have potential anticancer synergistic effects. Therefore, based on the application prospect of leucogen in preventing myelosuppression during chemotherapy for solid tumors, the study was designed to investigate the efficacy and safety of leucogen versus placebo on leukocyte and platelet whole-course management assisted by platinum plus low-dose long-term continuous intravenous infused 5-fluorouracil chemotherapy in the treatment of stage IV, recurrent or metastatic nasopharyngeal carcinoma.

Official Title
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A Multi-center, Randomized, Double-blind, Phase III Clinical Trial of Leucogen Versus Placebo on Leukocyte and Platelet Whole-course Management Assisted by Platinum Plus Low-dose Long-term Continuous Intravenous Infused 5-fluorouracil Chemotherapy in the Treatment of Stage IV, Recurrent or Metastatic Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma, Leucogen, Chemotherapy, Myelosuppression

Intervention / Treatment
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* Drug: 5-fu
* Drug: Lobaplatin
* Drug: Placebo
* Drug: leucogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old and ≤60 years old； Pathological diagnosis of stage IV, recurrent or distant metastatic nasopharyngeal carcinoma； Patients with stage IV, metastatic (including primary and secondary) or recurrent nasopharyngeal carcinoma who are not suitable for local treatment, local treatment mainly refers to measures related to anti-tumor therapy, including surgery, radiofrequency ablation, transhepatic artery chemoembolization (TACE), radiotherapy (excluding bone metastases, local moderate amount of radiation therapy for symptom relief without affecting hematological indicators)； Karnofsky functional status score should be at least 70 points (the decline of functional status score caused by tumor should be appropriately relaxed after the judgment of the researcher, and the minimum score should be no less than 50 points. ); At least 1 measurable lesion according to RECIST1.1 assessment criteria, measurable lesion should not have received local treatment such as radiotherapy; Expected survival ≥3 months; The function of vital organs meets the following requirements (not allowed within 14 days before screening . May use any blood components, cell growth factors, leukoplast, platelets Drugs, anemia correction drugs) : Neutrophil absolute count (ANC) ≥1.5×109/L Platelet ≥100×109/L; Hemoglobin ≥8.0g/ dL (note: Hemoglobin ≥8.0g/ dL can be achieved through blood transfusion or other intervention); Serum albumin ≥2.8g/dL; Bilirubin ≤ 1.5x ULN, ALT and AST≤ 1.5x ULN; ALT and AST≤ 5x ULN if liver metastasis was present; creatinine clearance ≥50mL/min Women of non-surgical sterilization or reproductive age and sexually active men enrolled in the study are required to use a medically effective form of contraception (such as an intrauterine device [IUD], birth control pills or condoms) for the duration of the study treatment and for at least 3 months after the last use of Tamfu and for at least 6 months after the last use of chemotherapy; The serum or urine HCG test of female patients of reproductive age who were not undergoing surgical sterilization must be negative within 7 days prior to study enrollment. And must be non lactation period; Informed consent has been signed. - Exclusion Criteria: Have a history of allergy to 5-FU, cisplatin and leucogen; Received elevated blood therapy 14 days prior to screening (including cytokines, leuk-lifting drugs, platelet-lifting drugs, anemia-correcting drugs, etc.) Major surgery other than nasopharyngeal cancer was diagnosed within 28 days prior to randomization or major surgery was expected during the study period; The subject has any active autoimmune disease or a history of autoimmune disease (e.g., but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism); Subjects with vitiligo or asthma in complete remission during childhood without any intervention as adults could be included; Subjects with asthma requiring medical intervention with bronchodilators were excluded); Subject is taking immunosuppressants, or systemic, or absorbable sites Hormone therapy to achieve immunosuppression (dose >10mg/ day prednisone or Other equally effective hormones) and continued to be used within 2 weeks prior to enrollment. The subject has previous or co-existing malignancies (except those that have been cured and survived for more than 5 years without cancer, such as basal cell carcinoma of the skin, carcinoma in situ of the cervix and papillary carcinoma of the thyroid); Patients with cardiac clinical symptoms or diseases that are not well controlled, such as: # HEART failure of NYHA grade 2 or above # unstable angina pectoris # myocardial infarction within 1 year # clinically significant ventricular arrhythmias or ventricular arrhythmias requiring treatment or intervention; Subjects have active infection or have unexplained fever >38.5 degrees during screening but before the first dose (the investigator judged that the subjects' fever due to tumor could be included in the study); Subjects with congenital or acquired immune deficiency (e.g. HIV infected), or active hepatitis (reference: HBsAg, anti-HBS, HBeAg, anti-HBC, anti-HBE, HBV DNA≥10#/ml, liver cell transaminase, etc.); Hepatitis C reference: HCV antibodies and HCVRNA); The subject has a known history of psychotropic drug abuse, alcoholism or drug abuse; In the judgment of the researcher, the subject has other factors that may lead to the termination of the study, such as other serious diseases (including mental diseases) requiring combined treatment, serious abnormal laboratory examination, family or social factors, which may affect the safety of the subject, or the collection of test data and samples. Women who are pregnant or breastfeeding, or who refuse/cannot accept medically acceptable conditions. For women with potential pregnancy and sexually active men. -

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Chemotherapy: 5-fu: 200mg/m2/d, continuous intravenous infusion on the 1st to 30th day of each cycle; Lobaplatin: 30mg/m2, used on the 1st and 28th day of each cycle; Q60d; Every 2 months for a treatment cycle, use 6 cycles, a total of 12 months. Drug: Placebo After diagnosis of stage IV, recurrent or metastatic nasopharyngeal carcinoma (within 3 weeks before treatment), placebo tablets were started,) 2 tablets/dose 3 times for peri-chemotherapy prophylaxis and inter-chemotherapy period, 3 tablets/dose 3 times daily during chemotherapy, and continued to be given orally 2 tablets/dose 3 times daily for 4 weeks after the end of chemotherapy. In case of grade III-IV myelosuppression during treatment, recombinant human granulocyte-stimulating factor injection (manufactured by Qilu Pharmaceutical Co., Ltd.) was given again at 2 5ug/kg, subcutaneously once daily, and the clinical trial was terminated. | Drug: 5-fu<br>* 5-fu: 200mg/m2/d, continuous intravenous infusion on the 1st to 30th day of each cycle.<br>Drug: Lobaplatin<br>* 30mg/m2, used on the 1st and 28th day of each cycle.<br>Drug: Placebo<br>* 2 tablets/dose 3 times for peri-chemotherapy prophylaxis and inter-chemotherapy period, 3 tablets/dose 3 times daily during chemotherapy, and continued to be given orally 2 tablets/dose 3 times daily for 4 weeks after the end of chemotherapy.<br>|
| Active Comparator: Experimental group<br>Chemotherapy: 5-fu: 200mg/m2/d, continuous intravenous infusion on the 1st to 30th day of each cycle; Lobaplatin: 30mg/m2, used on the 1st and 28th day of each cycle; Q60d; Every 2 months for a treatment cycle, use 6 cycles, a total of 12 months. Drug: Leucogen After the diagnosis of stage IV, recurrent or metastatic nasopharyngeal carcinoma (within 3 weeks before treatment), oral leucogen tablets (manufactured by JIANGSU JIBEIER PHARMACEUTICAL CO.,LTD, 20 mg/tablet) were started and 40 mg/dose was used 3 times for peri-chemotherapy prophylaxis and inter-chemotherapy period, and 60 mg/dose was used 3 times daily during chemotherapy, and 40 mg/dose was continued orally 3 times daily for 4 weeks after the end of chemotherapy. In case of grade III-IV myelosuppression during treatment, recombinant human granulocyte-stimulating factor injection (manufactured by Qilu Pharmaceutical Co., Ltd.) was given again at 2 5ug/kg, subcutaneously once daily, and the clinical trial was terminated. | Drug: 5-fu<br>* 5-fu: 200mg/m2/d, continuous intravenous infusion on the 1st to 30th day of each cycle.<br>Drug: Lobaplatin<br>* 30mg/m2, used on the 1st and 28th day of each cycle.<br>Drug: leucogen<br>* 40 mg/dose was used 3 times for peri-chemotherapy prophylaxis and inter-chemotherapy period, and 60 mg/dose was used 3 times daily during chemotherapy, and 40 mg/dose was continued orally 3 times daily for 4 weeks after the end of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic toxicity | Grade I-IV hematological toxicity | Up to 3 approximately months | 
| Time of myelosuppression | From the beginning of treatment to the onset of myelosuppression | Up to 3 approximately months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival | Up to 5 years | 
| PFS | Progression-free survival | Up to 5 years | 
| ORR | ORR | Up to 2 approximately years | 
| DCR | Disease control rate | Up to 2 approximately years | 
| DOR | Duration of response | Up to 2 approximately years |