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

Sponsor
Sun Yat-sen University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03925090
Collaborator
(none)
138
Enrollment
1
Location
2
Arms
45.8
Anticipated Duration (Months)
3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
138 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Dec 8, 2019
Anticipated Primary Completion Date :
Oct 1, 2021
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progress-free survival (PFS) [2 years]

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

    Secondary Outcome Measures

    1. Overall Survival (OS) [2 years]

      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. Locoregional Relapse-Free Survival (LRRFS) [2 years or until the date of the last follow-up visit.]

      Defined from date of randomization to date of first documentation of locoregional relapse or until the date of the last follow-up visit.

    3. Distant Metastasis-Free Survival (DMFS) [2 years]

      Defined from date of randomization to date of first documentation of distant metastases or until the date of the last followup visit.

    4. Objective Response Rate （ORR） [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).

    5. Incidence rate of adverse events (AEs) [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

    6. Correlation between the plasma EBV DNA level and PFS [2 years]

      The plasma EBV DNA level of the patients will be assessed.

    7. Correlation between pre-treatment PD-L1 expression level and PFS [2 years]

      Pre-treatment PD-L1 expression level is evaluated centrally by means of immunohistochemical testing.

    8. Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS [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.

    9. Change of QoL (quality of life) [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.

    10. Number of subjects with major pathologic response (MPR) [21-28 days]

      Major pathologic response rate (MPR) is defined as > 90% decrease in viable tumor.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Sun Yat-sen Universitty Cancer Center Guangzhou Guangdong China 510060

    Sponsors and Collaborators

    • Sun Yat-sen University

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Hai-Qiang Mai,MD,PhD, Deputy Director of the Department of Nasopharyngeal Carcinoma, Sun Yat-sen University
    ClinicalTrials.gov Identifier:
    NCT03925090
    Other Study ID Numbers:
    • B2019-014-01
    First Posted:
    Apr 23, 2019
    Last Update Posted:
    Apr 22, 2020
    Last Verified:
    Apr 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma
    Nasopharyngeal Carcinoma
    Cisplatin

    Study Results

    No Results Posted as of Apr 22, 2020