Immunotherapy and Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma

Chemotherapy Effect Clinical Trial

— RETICULA-NPC  

Official title:

Postponing or Omitting Re-irradiation After Tislelizumab Plus Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04921995
• Other study ID #: 2021052-1
• Status: Recruiting
• Phase: Phase 2
• Start date: April 15, 2019
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2022
• Source: Fudan University
• Contact: Xiaoshen Wang, MD.
• Phone: 0086-021-64377134
• Email: ruijin702[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multi-center, phase II trial to evaluate the safety and efficacy of postponing or omitting re-irradiation after systemic therapy with tislelizumab and chemotherapy in patients with unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. Patients who did not respond to or progressed on another ICI are allowed to receive tislelizumab rechallenge as a subgroup.

Description:

High dose reirradiation is usually recommended for unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. However, it potentially adds to the RT-related severe toxicities and deaths. This trial aims to investigate the feasibility of postponing or even omitting re-irradiation based on effective first-line systemic therapy with tislelizumab and chemotherapy. For patients that progressed after exposure to another PD-1 antibody,tislelizumab rechallenge is accepted as a second subgroup.In this trial, all patients will receive chemotherapy (on doctors' recommendation) and PD-1 antibody (tislelizumab 200mg every three weeks). Patients with no response to the systemic therapy will receive salvage low dose re-irradiation delivered by SBRT, while those who showed complete or partial response will continue maintenance therapy until progression, death or intolerable toxicity, and reirradiation will be postponed or omitted.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 30, 2024
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Diagnosed as local recurrence ± regional recurrence after =1 year of radical treatment;

2. Not suitable for surgery;

3. Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery.

4. ECOG score 0-1;

5. No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;

6. No contraindications to immunotherapy or chemoradiotherapy;

7. Adequate marrow function: WBC count = 3×10E9/L, NE count = 1.5×10E9/L, HGB = 90g/L, PLT count = 100×10E9/L;

8. Adequate liver function: ALT/AST = 2.5×ULN, TBIL = 2.0×ULN;

9. Adequate renal function: BUN/CRE = 1.5×ULN or endogenous creatinine clearance = 60ml/min (Cockcroft-Gault formula);

10. Take effective contraceptions during and two months after treatment;

11. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. Have local necrosis in recurrent lesions, estimated with bleeding risk;

2. Unexplained fever > 38.5 ?, except for tumor fever;

3. Treated with = 5 days antibiotics one month before enrollment;

4. Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);

5. Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA =10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;

6. Have =G3 late toxicities, except for skin, subcutaneous tissue or mucosa;

7. Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;

8. Have known allergy to large molecule protein products or any compound of study therapy;

9. Pregnant or breastfeeding;

10. Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;

11. Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapy Effect
• Immunotherapy
• Nasopharyngeal Carcinoma
• Recurrent Nasopharyngeal Carcinoma

Intervention

Drug:
• Tislelizumab
Chemotherapy (including but not limited to following): GP regimen: gemcitabine 1000mg/m2 d1, d8 + cisplatin 25 mg/m2 d1-3, every 3 weeks for 4-6 cycles; GX regimen: gemcitabine 800mg/m2 d1 + capecitabine 750 mg/m2 d1-14, every 3 weeks for 4-6 cycles. Capecitabine: 750 mg/m2 d1-14, every 3 weeks until unacceptable toxicities or patient's withdraw. anti-PD-1 antibody: Tislelizumab concurrently with chemotherapy: 200mg, every 3 weeks for 12 weeks. Tislelizumab in maintenance period: 200mg every 3 weeks or 400mg every 6 weeks, until one year or disease progression, or in the case of intolerable toxicities.

Locations

Country	Name	City	State
China	Eye and ENT Hospital of Fudan University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (3)

Kong F, Zhou J, Du C, He X, Kong L, Hu C, Ying H. Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma. BMC Cancer. 2018 Nov 20;18(1):1139. doi: 10.1186/s12885-018-5055-5. — View Citation

Liu LT, Chen QY, Tang LQ, Zhang L, Guo SS, Guo L, Mo HY, Zhao C, Guo X, Chen MY, Qian CN, Zeng MS, Hong MH, Shao JY, Sun Y, Ma J, Mai HQ. With or without reirradiation in advanced local recurrent nasopharyngeal carcinoma: a case-control study. BMC Cancer. 2016 Oct 7;16(1):774. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) .	3 months
Primary	Progress-free survival (PFS)	Defined from date of enrollment to date of first documentation of progression or death due to any cause.	2 year
Secondary	Overall survival (OS)	Defined from date of enrollment 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.	2 year
Secondary	Adverse events (AEs)	Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0	2 year
Secondary	Quality of life (QoL)	QoL scores were assessed by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30).	1 year

External Links

•   Eye and ENT Hospital of Fudan University homepage