Recurrent Nasopharyngeal CarcinomaPhase 2RETICULA-NPCNCT04921995
Immunotherapy and Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma
A Phase 2 study testing Tislelizumab in people with Recurrent Nasopharyngeal Carcinoma and Unresectable Nasopharyngeal Carcinoma, run by Fudan University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 15 to 90 years
- Conditions the study is for
- Recurrent Nasopharyngeal Carcinoma, Unresectable Nasopharyngeal Carcinoma, Chemotherapy Effect
- What is being tested?
- Tislelizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2019to 30 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Eye and ENT Hospital of Fudan University
Shanghai
Xiaoshen Wang, MD., ruijin702@163.com
About this study
Official title: Postponing or Omitting Re-irradiation After Tislelizumab Plus Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma
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.
Read the 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.
- Conditions
- Recurrent Nasopharyngeal Carcinoma, Unresectable Nasopharyngeal Carcinoma, Chemotherapy Effect, Immunotherapy, Stereotactic Body Radiation Therapy (SBRT)
- Being tested
- Tislelizumab
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | 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. Receives: Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) .
Measured: 3 months
Progress-free survival (PFS)
Defined from date of enrollment to date of first documentation of progression or death due to any cause.
Measured: 2 year
Secondary outcomes (3)
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.
Measured: 2 year
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
Measured: 2 year
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).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start15 Apr 2019
- Primary completion30 Oct 2022 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Recurrent Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaoshen Wang, Fudan University
- Investigators
- Xiaoshen Wang, Principal investigator, Eye & ENT Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921995
- Sponsor's protocol ID
- 2021052-1
- Acronym
- RETICULA-NPC
- Status last verified
- Mar 2022
- First submitted
- 7 Jun 2021
- Last updated
- 4 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 30453915Zhang 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.
PubMed 27567279Liu 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.
PubMed 27717335
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postponing or Omitting Re-irradiation After Tislelizumab Plus Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT04921995
- Acronym / sponsor ID
- RETICULA-NPC / 2021052-1
- Conditions
- Recurrent Nasopharyngeal Carcinoma, Unresectable Nasopharyngeal Carcinoma, Chemotherapy Effect, Immunotherapy, Stereotactic Body Radiation Therapy (SBRT)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 30 Oct 2022 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: TislelizumabMain 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. |
Who may qualify
- Ages
- 15 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tislelizumab1. 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. 2. 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. | Drug | Experimental |
Primary outcome
Objective response rate (ORR)
Time frame: 3 months
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)
Time frame: 2 year
Defined from date of enrollment to date of first documentation of progression or death due to any cause.
3 secondary outcomes
Overall survival (OS)
Time frame: 2 year
Adverse events (AEs)
Time frame: 2 year
Quality of life (QoL)
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Background: PubMed 30453915Kong 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.
- Background: PubMed 27567279Zhang 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.
- Background: PubMed 27717335Liu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaoshen Wang principal investigator
Eye & ENT Hospital of Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab in people with Recurrent Nasopharyngeal Carcinoma and Unresectable Nasopharyngeal Carcinoma, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaoshen Wang, MD. (0086-021-64377134, ruijin702@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04921995, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2022.