Phase II Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Combined With CCRT in NPC Patients

June 29, 2023 updated by: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Randomized, Placebo-controlled, Double-blind Phase II Clinical Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Immunotherapy Combined With Concurrent Chemoradiotherapy for High-risk Nasopharyngeal Carcinoma

This is a randomized Phase II trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with concurrent cisplatin chemoradiotherapy versus cisplatin concurrent chemoradiotherapy plus placebo in treating patients with high risk locoregionally advanced nasopharyngeal carcinoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. For locoregionally advanced NPC, especially for the high risk NPC (plasma EBV DNA ≥ 1500 copies/ml), the incidence of treatment failure is still high. Although concurrent chemoradiotherapy (CCRT) can improve the treatment outcomes of these patients, approximately 25% of locoregionally advanced NPCs still develop relapse and metastasis.

Hence, there is an urgent need for novel therapies to improve survival and reduce treatment-related toxicity in NPC patients. Accumulating evidence shows that PD-1 antibody is effective for treating recurrent/metastastic NPC patients. This is a Phase II randomized trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with CCRT versus CCRT plus placebo in treating patients with high risk NPC (Stage III-IVa, AJCC 8th and EBV DNA ≥ 1500 copies/ml).

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen Universitty Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III Original clinical staged as III-IVa （according to the 8th AJCC edition）
  2. No evidence of distant metastasis (M0)
  3. Plasm EB Virus DNA≥1500copies/ml
  4. Male and no pregnant female
  5. Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1
  6. WBC ≥ 4×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L
  7. With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 2.0×ULN)
  8. With normal renal function test ( creatinine clearance ≥60 ml/min)

Exclusion Criteria:

  1. Patients have evidence of relapse or distant metastasis
  2. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
  3. Receiving radiotherapy or chemotherapy previously
  4. The presence of uncontrolled life-threatening illness
  5. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  6. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
  7. Patients who have been treated with inhibitors of immune regulation (CTLA-4, PD-1, PD-L1, etc.).
  8. Patients with immunodeficiency disease and history of organ transplantation.
  9. Patients who have used large doses of glucocorticoids, anti-cancer monoclonal antibodies, and other immunosuppressive agents within 4 weeks.
  10. HIV positive.
  11. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
  12. Severe, uncontrolled medical conditions and infections.
  13. At the same time using other test drugs or in other clinical trials.
  14. Refusal or inability to sign informed consent to participate in the trial.
  15. Other treatment contraindications.
  16. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.
  17. Hepatitis B surface antigen (HBsAg) positive and HBVDNA ≥1000cps/ml.
  18. Patients with positive HCV antibody test results can only be included in the study when the polymerase chain reaction of HCV RNA is negative.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant and Adjuvant Toripalimab+CCRT
Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: Toripalimab Toripalimab 240mg every 2 weeks with a total of 2 cycles as neoadjuvant anti-PD-1 immunotherapy; Toripalimab240mg every 3 weeks with a total of 8 cycles as adjuvant anti-PD-1 immunotherapy 2 weeks after CCRT Other Names:anti-PD-1 antibody, JS001
Drug: Cisplatin+Toripalimab
chemotherapy and monoclonal antibody
Other Names:
  • DDP+ JS001
Placebo Comparator: Neoadjuvant and Adjuvant Placebo+CCRT
Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: placebo placebo 240mg every 2 weeks with a total of 2 cycles as neoadjuvant treatment; placebo 240mg every 3 weeks with a total of 8 cycles as adjuvant treatment 2 weeks after CCRT.
Drug: Cisplatin+placebo
chemotherapy
Other Names:
  • DDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progress-free survival (PFS)
Time Frame: 2 years
Defined from date of randomization to date of first documentation of progression or death due to any cause, whichever occurred first.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence rate of adverse events (AEs)
Time Frame: 2 years
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 years
Objective Response Rate （ORR）
Time Frame: After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI).
After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment
Correlation between the plasma EBV DNA level and PFS
Time Frame: 2 years
The plasma EBV DNA level of the patients will be assessed.
2 years
Correlation between pre-treatment PD-L1 expression level and PFS
Time Frame: 2 years
Pre-treatment PD-L1 expression level is evaluated centrally by means of immunohistochemical testing.
2 years
Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS
Time Frame: 2 years
TILs are lymphoid cells (T cells) that infiltrate solid tumors (intra-tumoral TILs) and stroma (stromal TILs), which play important roles in the tumor microenvironment.
2 years
Change of QoL (quality of life)
Time Frame: 1 year
QoL scores were assessed by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before neoadjuvant PD-1 antibody, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy.
1 year
Number of subjects with major pathologic response (MPR)
Time Frame: 21-28 days
Major pathologic response rate (MPR) is defined as > 90% decrease in viable tumor.
21-28 days
Overall Survival (OS)
Time Frame: 2 years
Defined as the time from randomisation to death.
2 years
Locoregional Relapse-Free Survival (LRRFS)
Time Frame: 2 years or until the date of the last follow-up visit.
Defined as the time from the randomisation to documented locoregional recurrence or death due to any cause.
2 years or until the date of the last follow-up visit.
Distant Metastasis-Free Survival (DMFS)
Time Frame: 2 years
Defined as the time from randomisation to documented distant metastasis or death due to any cause.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Overall Study Officials Mai, MD,PhD, Sun Yat-sen University Cancer Cente

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2019

Primary Completion (Actual)

December 6, 2021

Study Completion (Estimated)

October 1, 2023

Study Registration Dates

First Submitted

March 28, 2019

First Submitted That Met QC Criteria

April 20, 2019

First Posted (Actual)

April 23, 2019

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 29, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2019-014-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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