Comparing Chemotherapy With/Without Toripalimab For Primary Metastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The aim of this study is to compare the efficacy of Toripalimab Combined with GP Regimen Chemotherapy Versus GP Regimen Chemotherapy for Primary Metastatic NPC.

Detailed Description
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About 4-10% of patients with nasopharyngeal carcinoma (NPC) have metastatic disease at diagnosis. The treatment recommendation of primary metastatic NPC is systemic chemotherapy. However, the optimal regimen is yet to determine due to lack of prospective randomized trial for this unique group of patients. Generally, GP regimen is used as the first-line treatment of primary metastatic NPC. The aim of this study is to compare the efficacy of Toripalimab Combined with GP Regimen Chemotherapy Versus GP Regimen Chemotherapy for Primary Metastatic NPC.

Official Title
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Phase II Study of Comparing Toripalimab Combined With GP Regimen Chemotherapy Versus GP Regimen Chemotherapy for Primary Metastatic Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Radiation: IMRT to the nasopharynx and neck
* Drug: Gemcitabine and Cisplatin Chemotherapy
* Drug: Adjuvant chemotherapy with Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign an informed consent; Age older than 18 years old and younger than 70 years old; Patients with newly histologically confirmed primary metastatic nasopharyngeal carcinoma; At least one metastatic site that fulfills the criteria of Evaluable Disease per RECIST 1.1 Criteria; Anticipated overall survival more than 3 months; Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1; No primary treatment of radiation, surgery, chemotherapy, targeted therapy and immune therapy post diagnosis of NPC; Neutrophil ≥ 1.5×109 /L and PLT ≥100×109 /L and HGB ≥90 g/L; With normal liver function test (ALT、AST ≤ 3×ULN, TBIL≤ 1.5×ULN, Albumin≥2.8g/dL ); With normal renal function test (Creatinine ≤ 1.5 ×ULN and creatinine clearance ≥60 ml/min); HBV DNA<500 IU/mL（or 2500 copies/mL）and HCV RNA negative ; Male and no pregnant female, able to adapt birth control methods during treatment. Exclusion Criteria: Hypersensitivity to Toripalimab, Gemcitabine, Cisplatin and Capecitabine; Symptomatic spinal cord compression, or high-risk to develop pathological fracture that requires urgent surgery or radiation; Necrotic disease, high-risk of massive nasal bleeding; Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years; Receive vaccine or live vaccine within 30 days prior to signing the informed consent; Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent; Severe, uncontrolled medical conditions and infections; Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy; vitiligo or inactive asthma who don't need systemic therapy can recruit; History of interstitial lung disease; HIV positive; Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥500IU/ml, or 2500cps/ml; Positive HCV RNA; Other diseases which may influence the safety or compliance of the clinical trial, such as heart failure with symptom, unstable angina, myocardial infarction, active infections those need systemic therapy, mental illness, or their family and society factors; Women of child-bearing potential who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Toripalimab Combined with GP Arm<br>Systemic chemotherapy for 6 cycles: Toripalimab 240mg d1+Gemcitabine 1.0g/m2 d1, Cisplatin 80mg/m2 d1, q3w; Followed by Radiotherapy to the nasopharynx and neck; Then maintenance therapy of Toripalimab with Capecitabine: Toripalimab 240mg d1+Capecitabine 1000mg/m2 bid d1-14, q3w | Drug: Toripalimab<br>* PD-1 inhibitor<br>* Other names: JS001;Radiation: IMRT to the nasopharynx and neck<br>* IMRT to the nasopharynx and neck<br>* Other names: RT to the nasopharynx and neck;Drug: Gemcitabine and Cisplatin Chemotherapy<br>* Systemic chemotherapy<br>* Other names: GP regimen chemotherapy;Drug: Adjuvant chemotherapy with Capecitabine<br>* Adjuvant chemotherapy after radiation<br>* Other names: Xeloda;|
| Active Comparator: GP Arm<br>Systemic chemotherapy for 6 cycles: Gemcitabine 1.0g/m2 d1, Cisplatin 80mg/m2 d1, q3w; Followed by Radiotherapy to the nasopharynx and neck; Then maintenance therapy of Capecitabine: Capecitabine 1000mg/m2 bid d1-14, q3w | Radiation: IMRT to the nasopharynx and neck<br>* IMRT to the nasopharynx and neck<br>* Other names: RT to the nasopharynx and neck;Drug: Gemcitabine and Cisplatin Chemotherapy<br>* Systemic chemotherapy<br>* Other names: GP regimen chemotherapy;Drug: Adjuvant chemotherapy with Capecitabine<br>* Adjuvant chemotherapy after radiation<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate of Systemic chemotherapy | ORR according to RECIST 1.1 Criteria | At the end of Cycle 6 of chemotherapy (each cycle is 21days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate of Systemic chemotherapy | DCR according to RECIST 1.1 Criteria | At the end of Cycle 6 of chemotherapy (each cycle is 21days) | 
| The proportion of patients received radiotherapy to nasopharynx | Only patients with disease control after systemic chemotherapy will receive radiotherapy | 2 year | 
| Progression-free Survival | Defined from date of randomization to date of first documentation of progression or death due to any cause. | 5 year | 
| Overall Survival | Defined from date of randomization to date of first documentation of death from Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up. | 5 year | 
| Progression-free Survival Rate | Defined from date of randomization to date of first documentation of progression or death due to any cause. | 1 year, 2 year rates | 
| Overall Survival Rate | Defined from date of randomization to date of first documentation of death from Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up. | 1 year, 2 year rates | 
| the Incidence of Adverse Effect | According to CTCAE 4.0.03 | 1 year | 
| Changes of Quality of life, according to EORTC QLQ-C30 | According to EORTC QLQ-C30 | 1 year | 
| Changes of Quality of life, according to EORTC QLQ-H&N35 | According to EORTC QLQ-H&N35 | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, Primary metastatic, de novo metastatic, Toripalimab, PD-1, Immune checkpoint inhibitor, Chemotherapy