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Cadonilimab (PD-1/CTLA-4 Bi-specific Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma

Sponsor
Sun Yat-sen University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05587374
Collaborator
Akeso Pharmaceuticals, Inc. (Other)
418
Enrollment
13
Locations
2
Arms
48
Anticipated Duration (Months)
32.2
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The trial aimed to compare cadonilimab combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in high-risk locoregionally-advanced nasopharyngeal carcinoma (LANPC).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The trial plans to enroll patients with stage III-IVA (AJCC 8th, except T3N0-1 or T4N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus cadonilimab in induction chemotherapy and adjuvant chemotherapy. All patients will receive intensity-modulated radiotherapy (IMRT). Cadonilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 14 cycles in adjuvant therapy.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
418 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Cadonilimab (PD-1/CTLA-4 Bi-specific Antibody) Combined With Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma: a Randomized, Controlled, Multicenter, Phase 3 Clinical Trial
Anticipated Study Start Date :
Jan 1, 2023
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jan 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cadonilimab arm

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.

Drug: Cadonilimab
Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
Other Names:
  • PD-1/CTLA-4 bi-specific antibody

    • Drug: Gemcitabine
    Gemcitabine 1g/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 2 cycles during radiation
    Other Names:
  • DDP

    • Radiation: Intensity-modulated radiotherapy
    Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
    Other Names:
  • IMRT

    		•
    Active Comparator: Chemoradiation arm

    Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.

    Drug: Gemcitabine
    Gemcitabine 1g/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 2 cycles during radiation
    Other Names:
  • DDP

    • Radiation: Intensity-modulated radiotherapy
    Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
    Other Names:
  • IMRT

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Failure-free survival (FFS) [3 years]

      calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.

    Secondary Outcome Measures

    1. Overall survival (OS) [3 years]

      calculated from randomization to the date of death from any cause.

    2. Distant metastasis-free survival (DMFS) [3 years]

      calculated from randomization to the date of first distant metastasis.

    3. Locoregional recurrence-free survival (LRRFS) [3 years]

      calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.

    4. Adverse events (AEs) and serious adverse events (SAEs) [3 years]

      Graded according to CTCAE V5.0.

    5. Quality of life (QoL) [3 years]

      The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.

    6. Failure-free survival (FFS) within different subgroups [3 years]

      analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (≤4000copies/ml vs. >4000copies/ml), different PD-L1 expression levels, age, gender, performance status, T category, N category, and stage (III vs. IVA).

    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 histologically confirmed nasopharyngeal carcinoma.

    2. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).

    3. Eastern Cooperative Oncology Group performance status ≤1.

    4. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.

    5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.

    6. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).

    7. Patients must be informed of the investigational nature of this study and give written informed consent.

    8. 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 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

    Exclusion Criteria:

    1. Age > 65 or < 18.

    2. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml

    3. Hepatitis C virus (HCV) antibody positive

    4. 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).

    5. Has any condition that required systemic corticosteroid (equivalent to prednisone

    10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.

    1. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.

    2. Has a known history of interstitial lung disease.

    3. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.

    4. Is pregnant or breastfeeding.

    5. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.

    6. Has known allergy to large molecule protein products or any compound of cadonilimab.

    7. Has a known history of human immunodeficiency virus (HIV) infection.

    8. Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The First Affiliated Hospital of Bengbu Medical College Bengbu Anhui China 233000
    2 The First Affiliated Hospital of University of Science and Technology of China Hefei Anhui China 230041
    3 Sun Yat-sen Memorial Hospital Guangzhou Guangdong China 510000
    4 SUN YAT-SEN UNIVERSITY cANCER CENTER Guangzhou Guangdong China 510060
    5 Shenzhen People's Hospital Shenzhen Guangdong China 518001
    6 Cancer Hospital of Guangxi Medical University Nanning Guangxi China
    7 Cancer Hospital of Guizhou Medical University Guiyang Guizhou China
    8 Renmin Hospital of Wuhan University Wuhan Hubei China 430000
    9 Zhongnan Hospital of Wuhan University Wuhan Hubei China 430071
    10 Hubei Province Cancer Hosiptal Wuhan Hubei China
    11 Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China
    12 Hunan Cancer Hospital Changsha Hunan China 410000
    13 Xiangya Hospital Central South University Changsha Hunan China

    Sponsors and Collaborators

    • Sun Yat-sen University
    • Akeso Pharmaceuticals, Inc.

    Investigators

    • Principal Investigator: Jun Ma, M.D., Sun Yat-sen University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jun Ma, MD, Professor, Sun Yat-sen University
    ClinicalTrials.gov Identifier:
    NCT05587374
    Other Study ID Numbers:
    • AK104-IIT-019
    First Posted:
    Oct 20, 2022
    Last Update Posted:
    Dec 14, 2022
    Last Verified:
    Dec 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jun Ma, MD, Professor, Sun Yat-sen University
    immunotherapy
    PD-1/CTLA-4 Bi-specific Antibody
    Chemoradiotherapy
    Additional relevant MeSH terms:
    Carcinoma
    Nasopharyngeal Carcinoma
    Nasopharyngeal Neoplasms
    Gemcitabine
    Cisplatin
    Antibodies, Bispecific

    Study Results

    No Results Posted as of Dec 14, 2022