Comparing Chemotherapy With/Without Toripalimab For Primary Metastatic Nasopharyngeal Carcinoma

NCT04517214 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: TRANSFORM
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; Primary metastatic; de novo metastatic; Toripalimab; PD-1; Immune checkpoint inhibitor; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS, defined as the time from randomization to the first documented objective tumor progression or death from any cause

  5 year

Secondary Outcomes (9)

• Objective Response Rate of Systemic chemotherapy

  At the end of Cycle 6 of chemotherapy (each cycle is 21 days)

• Disease Control Rate of Systemic chemotherapy

  At the end of Cycle 6 of chemotherapy (each cycle is 21days)

• The proportion of patients received radiotherapy to nasopharynx

  2 year

• Overall Survival

  5 year

• Progression-free Survival Rate

  1 year, 2 year rates

Study Arms (2)

Toripalimab Combined with GP Arm

EXPERIMENTAL

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; Radiation: IMRT to the nasopharynx and neck; Drug: Gemcitabine and Cisplatin Chemotherapy; Drug: Adjuvant chemotherapy with Capecitabine

GP Arm

ACTIVE COMPARATOR

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; Drug: Gemcitabine and Cisplatin Chemotherapy; Drug: Adjuvant chemotherapy with Capecitabine

Interventions

Toripalimab DRUG

PD-1 inhibitor

Also known as: JS001

Toripalimab Combined with GP Arm

IMRT to the nasopharynx and neck RADIATION

IMRT to the nasopharynx and neck

Also known as: RT to the nasopharynx and neck

GP Arm; Toripalimab Combined with GP Arm

Gemcitabine and Cisplatin Chemotherapy DRUG

Systemic chemotherapy

Also known as: GP regimen chemotherapy

GP Arm; Toripalimab Combined with GP Arm

Adjuvant chemotherapy with Capecitabine DRUG

Adjuvant chemotherapy after radiation

Also known as: Xeloda

GP Arm; Toripalimab Combined with GP Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Xiaomin Ou

Shanghai, 200032, China

Location

Related Publications (10)

• 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.

  PMID: 26506872 BACKGROUND

• 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.

  PMID: 26485757 BACKGROUND

• 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.

  PMID: 24630534 BACKGROUND

• 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.

  PMID: 24635574 BACKGROUND

• 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.

  PMID: 26321262 BACKGROUND

• 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.

  PMID: 28391025 BACKGROUND

• 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.

  PMID: 30665378 BACKGROUND

• Chua DT, Sham JS, Au GK. A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral Oncol. 2005 Jul;41(6):589-95. doi: 10.1016/j.oraloncology.2005.01.008. Epub 2005 Apr 14.

  PMID: 15975521 BACKGROUND

• 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.

  PMID: 27567279 BACKGROUND

• 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.

  PMID: 30213452 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

toripalimab; Gemcitabine; Chemotherapy, Adjuvant; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Combined Modality Therapy; Therapeutics; Drug Therapy; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Chaosu Hu, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of Department of Radiation Oncology, Clinical Professor

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 18, 2020
• Study Start: November 1, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)