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Immunotherapy and Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma (RETICULA-NPC)

Primary Purpose

Recurrent Nasopharyngeal Carcinoma, Unresectable Nasopharyngeal Carcinoma, Chemotherapy Effect

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Tislelizumab

About this trial

This is an interventional treatment trial for Recurrent Nasopharyngeal Carcinoma

Eligibility Criteria

15 Years - 90 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment;
Not suitable for surgery;
Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery.
ECOG score 0-1;
No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
No contraindications to immunotherapy or chemoradiotherapy;
Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
Take effective contraceptions during and two months after treatment;
Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

Have local necrosis in recurrent lesions, estimated with bleeding risk;
Unexplained fever > 38.5 ℃, except for tumor fever;
Treated with ≥ 5 days antibiotics one month before enrollment;
Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);
Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;
Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
Have known allergy to large molecule protein products or any compound of study therapy;
Pregnant or breastfeeding;
Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
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.

Sites / Locations

Eye and ENT Hospital of Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

Main group: Patients will be given first line tislelizumab plus investigator's choice chemotherapy, with re-irradiation postponed or omitted. Subgroup: For patients that progressed after exposure to another PD-1 antibody, tislelizumab rechallenge combined with either low dose SBRT or low dose gemcitabine and metronomic capecitabine is accepted as a second subgroup.

Outcomes

Primary Outcome Measures

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) .

Progress-free survival (PFS)

Defined from date of enrollment to date of first documentation of progression or death due to any cause.

Secondary Outcome Measures

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.

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

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).

Full Information

NCT ID

NCT04921995

First Posted

June 7, 2021

Last Updated

March 23, 2022

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04921995

Brief Title

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

Acronym

RETICULA-NPC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 15, 2019 (Actual)

Primary Completion Date

October 30, 2022 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Nasopharyngeal Carcinoma, Unresectable Nasopharyngeal Carcinoma, Chemotherapy Effect, Immunotherapy, Stereotactic Body Radiation Therapy (SBRT)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Main group: Patients with unresectable, recurrent NPC who were treated with tislelizumab plus investigator's choice chemotherapy, with re-irradiation postponed or omitted. But there are two subgroups, one subgroup was ICI naive patients and were given first line tislelizumab plus investigator's choice chemotherapy. The other subgroup included patients who displayed no response to or progressed after previous PD-1 blockade, and were treated with tislelizumab rechallenge plus either chemotherapy or low dose SBRT.

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tislelizumab

Intervention Description

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.

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

Defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) .

Time Frame

3 months

Title

Progress-free survival (PFS)

Description

Defined from date of enrollment to date of first documentation of progression or death due to any cause.

Time Frame

2 year

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

Time Frame

2 year

Title

Adverse events (AEs)

Description

Time Frame

2 year

Title

Quality of life (QoL)

Description

QoL scores were assessed by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30).

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment; Not suitable for surgery; Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery. ECOG score 0-1; No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy; No contraindications to immunotherapy or chemoradiotherapy; Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L; Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN; Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula); Take effective contraceptions during and two months after treatment; Patients must be informed of the investigational nature of this study and give written informed consent. Exclusion Criteria: Have local necrosis in recurrent lesions, estimated with bleeding risk; Unexplained fever > 38.5 ℃, except for tumor fever; Treated with ≥ 5 days antibiotics one month before enrollment; Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy); Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive; Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa; Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment; Have known allergy to large molecule protein products or any compound of study therapy; Pregnant or breastfeeding; Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma; 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xiaoshen Wang, MD.

Phone

0086-021-64377134

ruijin702@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiaoshen Wang

Organizational Affiliation

Eye and ENT Hospital of Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Eye and ENT Hospital of Fudan University

City

Shanghai

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaoshen Wang, MD.

ruijin702@163.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

30453915

Citation

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.

Results Reference

background

PubMed Identifier

27567279

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.

Results Reference

background

PubMed Identifier

27717335

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. doi: 10.1186/s12885-016-2803-2.

Results Reference

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

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