NCT06712888

Brief Summary

The main questions it aims to answer are:

  1. 1.Does the combination of GP induction chemotherapy and toripalimab improve the 3-year progression-free survival (PFS) compared to GP induction chemotherapy with placebo?
  2. 2.What are the differences in CR after induction therapy, 3-year overall survival (OS), locoregional progression, and distant progression between the two groups?
  3. 3.What are the differences in safety between the two groups?
  4. 4.Are there predictive biomarkers of therapeutic efficacy, such as changes in EBV DNA or immune parameters, that correlate with treatment outcomes?

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
466

participants targeted

Target at P50-P75 for phase_3

Timeline
69mo left

Started Feb 2025

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress18%
Feb 2025Jan 2032

First Submitted

Initial submission to the registry

November 25, 2024

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 2, 2024

Completed
3 months until next milestone

Study Start

First participant enrolled

February 17, 2025

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2030

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2032

Last Updated

March 18, 2025

Status Verified

March 1, 2025

Enrollment Period

4.9 years

First QC Date

November 25, 2024

Last Update Submit

March 17, 2025

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

Nasopharyngeal CarcinomaAnti-PD-1 therapyinduction chemotherapy

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival

    Defined as the time from randomisation to first progression (locoregional or distant) or death, whichever occurred first.

    3 years

Secondary Outcomes (5)

  • Overall Survival

    3 years

  • Locoregional Progression

    3 years

  • Distant Progression

    3 years

  • Complete Response Rate

    9 weeks

  • Incidence of Acute and Late Toxicity

    3 years

Other Outcomes (1)

  • The correlation of pre-treatement plasma EBV DNA and dynamic change after induction therapy between with the PFS

    3 years

Study Arms (2)

Induction GP+placebo group

ACTIVE COMPARATOR

GP + Placebo Induction Therapy: Gemcitabine: 1000 mg/m² on days 1 and 8 DDP (cisplatin): 80 mg/m² on day 1 Placebo: 240 mg on day 1 Total of 3 cycles. Concurrent Chemoradiotherapy (CCRT): DDP (cisplatin): 100 mg/m² on day 1 of radiation, then every 3 weeks during radiotherapy. Total of 3 cycles (administered on D1, D22, and D43). Adjuvant Metronomic Capecitabine Therapy: Starts 4-6 weeks after the completion of radiotherapy and continues for up to 1 year. Adjuvant metronomi capecitabine is administered at the physician's discretion: Capecitabine: 650 mg/m², administered BID (twice daily).

Drug: GP plus placebo induction therapy

Induction GP+toripalimab group

EXPERIMENTAL

Induction GP + Toripalimab Therapy: Gemcitabine: 1000 mg/m² on days 1 and 8 DDP (cisplatin): 80 mg/m² on day 1 Toripalimab: 240 mg on day 1 Total of 3 cycles. Concurrent Chemoradiotherapy (CCRT): DDP (cisplatin): 100 mg/m² on day 1 of radiation, then every 3 weeks during radiotherapy. Total of 3 cycles (administered on D1, D22, and D43). Adjuvant Metronomic Capecitabine Therapy: Starts 4-6 weeks after the completion of radiotherapy and continues for up to 1 year. Adjuvant metronomic capecitabine therapy is administered at the physician's discretion: Capecitabine: 650 mg/m², administered BID (twice daily).

Drug: TORIPALIMAB INJECTION (JS001 ) combine with GP chemotherapy

Interventions

TORIPALIMAB INJECTION (JS001 ) combine with GP chemotherapyDRUG

Drug: Toripalimab 240mg will be given every 3 weeks for 3 cycles, started on day 1 of induction chemotherapy. Other Names: JS001 PD-1 antibody Drug: Gemcitabine 1000mg/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 3 cycles during radiation Other Names: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 70 Gy will be given in 33 fractions. Other Names: IMRT

Induction GP+toripalimab group
GP plus placebo induction therapyDRUG

Drug: Placebo 240mg will be given every 3 weeks for 3 cycles, started on day 1 of induction chemotherapy. Drug: Gemcitabine 1000mg/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 3 cycles during radiation Other Names: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 70 Gy will be given in 33 fractions. Other Names: IMRT

Induction GP+placebo group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Voluntarily participates and signs an informed consent form.
  • Aged 18-70 years, male or non-pregnant female.
  • Pathologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, i.e., WHO Type II or III).
  • Staging of any T, N2-3 or T4N1 (9th AJCC/UICC staging), with no distant metastasis.
  • ECOG performance status score of 0-1.
  • Hemoglobin (HGB) ≥90 g/L, neutrocyte count≥1.5×10⁹/L, platelets (PLT) ≥100×10⁹ /L.
  • Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
  • Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
  • Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.

You may not qualify if:

  • Age \> 70 years or \< 18 years.
  • Patients with recurrence or distant metastases.
  • Pathologically confirmed nasopharyngeal keratinizing squamous cell carcinoma (WHO Type I).
  • Patients who have previously undergone radiotherapy or systemic chemotherapy.
  • Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA \>1000 copies/ml or 200IU/ml.
  • Hepatitis C virus (HCV) antibody positive.
  • Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
  • Has any condition that required systemic corticosteroid (equivalent to prednisone \>10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients who received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroids will be allowed.
  • Has a known history of active bacillus tuberculosis within 1 year; patients with adequately treated active bacillus tuberculosis over 1 year ago will be allowed.
  • Has a known history of interstitial lung disease.
  • Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
  • Is pregnant or breastfeeding.
  • Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer and papillary thyroid carcinoma.
  • Has known allergy to large molecule protein products or any compound of toripalimab.
  • Has a known history of human immunodeficiency virus infection.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

  • Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.

    PMID: 34341578BACKGROUND

  • Chen YP, Liu X, Zhou Q, Yang KY, Jin F, Zhu XD, Shi M, Hu GQ, Hu WH, Sun Y, Wu HF, Wu H, Lin Q, Wang H, Tian Y, Zhang N, Wang XC, Shen LF, Liu ZZ, Huang J, Luo XL, Li L, Zang J, Mei Q, Zheng BM, Yue D, Xu J, Wu SG, Shi YX, Mao YP, Chen L, Li WF, Zhou GQ, Sun R, Guo R, Zhang Y, Xu C, Lv JW, Guo Y, Feng HX, Tang LL, Xie FY, Sun Y, Ma J. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021 Jul 24;398(10297):303-313. doi: 10.1016/S0140-6736(21)01123-5. Epub 2021 Jun 7.

    PMID: 34111416BACKGROUND

  • Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

    PMID: 31150573BACKGROUND

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PMID: 30207593BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNasopharyngeal NeoplasmsPharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsHead and Neck NeoplasmsNeoplasms by SiteNasopharyngeal DiseasesPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Central Study Contacts

Hai-Qiang Mai, Ph. D.

CONTACT

+86-020-87343643maihq@sysucc.org.cn

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

November 25, 2024

First Posted

December 2, 2024

Study Start

February 17, 2025

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

January 1, 2032

Last Updated

March 18, 2025

Record last verified: 2025-03

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)