Comparing Chemotherapy With/Without Toripalimab For Primary Metastatic Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04517214
• Other study ID #: TRANSFORM
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: July 2021
• Source: Fudan University
• Contact: Chaosu Hu, M.D.
• Phone: +8621-64175590
• Email: hucsu62[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Sign an informed consent;

2. Age older than 18 years old and younger than 70 years old;

3. Patients with newly histologically confirmed primary metastatic nasopharyngeal carcinoma;

4. At least one metastatic site that fulfills the criteria of "Evaluable Disease" per RECIST 1.1 Criteria;

5. Anticipated overall survival more than 3 months;

6. Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;

7. No primary treatment of radiation, surgery, chemotherapy, targeted therapy and immune therapy post diagnosis of NPC;

8. Neutrophil = 1.5×109 /L and PLT =100×109 /L and HGB =90 g/L;

9. With normal liver function test (ALT?AST = 3×ULN, TBIL= 1.5×ULN, Albumin=2.8g/dL );

10. With normal renal function test (Creatinine = 1.5 ×ULN and creatinine clearance =60 ml/min);

11. HBV DNA<500 IU/mL(or 2500 copies/mL)and HCV RNA negative ;

12. Male and no pregnant female, able to adapt birth control methods during treatment.

Exclusion Criteria:

1. Hypersensitivity to Toripalimab, Gemcitabine, Cisplatin and Capecitabine;

2. Symptomatic spinal cord compression, or high-risk to develop pathological fracture that requires urgent surgery or radiation;

3. Necrotic disease, high-risk of massive nasal bleeding;

4. Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years;

5. Receive vaccine or live vaccine within 30 days prior to signing the informed consent;

6. Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent;

7. Severe, uncontrolled medical conditions and infections;

8. 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;

9. History of interstitial lung disease;

10. HIV positive;

11. Hepatitis B surface antigen (HBsAg) positive and HBV-DNA =500IU/ml, or 2500cps/ml; Positive HCV RNA;

12. 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;

13. Women of child-bearing potential who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Toripalimab
PD-1 inhibitor

Radiation:
• IMRT to the nasopharynx and neck
IMRT to the nasopharynx and neck

Drug:
• Gemcitabine and Cisplatin Chemotherapy
Systemic chemotherapy
• Adjuvant chemotherapy with Capecitabine
Adjuvant chemotherapy after radiation

Locations

Country	Name	City	State
China	Xiaomin Ou	Shanghai

Sponsors (13)

Lead Sponsor

Collaborator

Fudan University

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Anhui Provincial Hospital, Cancer Hospital of Chinese Academy of Medical Science, Shenzhen Center, First Affiliated Hospital of Xi'anJiaotong Univerisity, Fudan University Eye and ENT Hospital, Guangzhou Panyu Central Hospital, Hangzhou Cancer Hospital, Nanfang Hospital of Southern Medical University, Ningbo Medical Center Lihuili Hospital, Shenzhen People's Hospital, Sir Run Run Shaw Hospital, The First People's Hospital of Changzhou

Country where clinical trial is conducted

China, 

References & Publications (10)

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Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal carcinoma. Lancet. 2016 Mar 5;387(10022):1012-1024. doi: 10.1016/S0140-6736(15)00055-0. Epub 2015 Aug 28. Review. — View Citation

Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10. — View Citation

Jiang F, Jin T, Feng XL, Jin QF, Chen XZ. Long-term outcomes and failure patterns of patients with nasopharyngeal carcinoma staged by magnetic resonance imaging in intensity-modulated radiotherapy era: The Zhejiang Cancer Hospital's experience. J Cancer Res Ther. 2015 Oct;11 Suppl 2:C179-84. doi: 10.4103/0973-1482.168181. — View Citation

Lang J, Gao L, Guo Y, Zhao C, Zhang C; Society of Head & Neck Tumor Surgery; Society of Radiation Therapy; Chinese Anti-Cancer Association. Comprehensive treatment of squamous cell cancer of head and neck: Chinese expert consensus 2013. Future Oncol. 2014;10(9):1635-48. doi: 10.2217/fon.14.44. Epub 2014 Mar 17. — View Citation

Lee AW, Ng WT, Chan LL, Hung WM, Chan CC, Sze HC, Chan OS, Chang AT, Yeung RM. Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014 Mar;110(3):377-84. doi: 10.1016/j.radonc.2014.02.003. Epub 2014 Mar 11. Review. — View Citation

Ou X, Zhou X, Shi Q, Xing X, Yang Y, Xu T, Shen C, Wang X, He X, Kong L, Ying H, Hu C. Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost. Oncotarget. 2015 Nov 10;6(35):38381-97. doi: 10.18632/oncotarget.5420. — View Citation

Sun XS, Liu LT, Liu SL, Guo SS, Wen YF, Xie HJ, Tang QN, Liang YJ, Li XY, Yan JJ, Ma J, Chen QY, Tang LQ, Mai HQ. Identifying optimal candidates for local treatment of the primary tumor among patients with de novo metastatic nasopharyngeal carcinoma: a retrospective cohort study based on Epstein-Barr virus DNA level and tumor response to palliative chemotherapy. BMC Cancer. 2019 Jan 21;19(1):92. doi: 10.1186/s12885-019-5281-5. — View Citation

Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23. Erratum in: Lancet. 2016 Oct 15;388(10054):1882. — View Citation

Zou X, You R, Liu H, He YX, Xie GF, Xie ZH, Li JB, Jiang R, Liu LZ, Li L, Zhang MX, Liu YP, Hua YJ, Guo L, Qian CN, Mai HQ, Chen DP, Luo Y, Shen LF, Hong MH, Chen MY. Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer. 2017 May;77:117-126. doi: 10.1016/j.ejca.2017.02.029. Epub 2017 Apr 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	The proportion of patients received radiotherapy to nasopharynx	Only patients with disease control after systemic chemotherapy will receive radiotherapy	2 year
Secondary	Progression-free Survival	Defined from date of randomization to date of first documentation of progression or death due to any cause.	5 year
Secondary	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
Secondary	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
Secondary	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
Secondary	the Incidence of Adverse Effect	According to CTCAE 4.0.03	1 year
Secondary	Changes of Quality of life, according to EORTC QLQ-C30	According to EORTC QLQ-C30	1 year
Secondary	Changes of Quality of life, according to EORTC QLQ-H&N35	According to EORTC QLQ-H&N35	1 year