Concurrent and Adjuvant PD-1 Blockade Combined With Induction Chemotherapy Plus Radiotherapy in Nasopharyngeal Carcinoma (PLATINUM)

February 3, 2024 updated by: Jun Ma, MD, Sun Yat-sen University

Whole-course Concurrent and Adjuvant Nivolumab Combined With Induction Chemotherapy Followed by Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase 2, Multi-center, Single-arm Clinical Trial

This is a phase 2, single-arm, multicenter clinical trial, with the purpose to evaluate the therapeutic efficacy and safety of PD-1 Blockade combined with induction chemotherapy and radiotherapy alone in high-risk locoregionally advanced nasopharyngeal carcinoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This phase 2, single-arm, multicenter clinical trial plans to enroll 146 patients with newly-diagnosed, pathologically-proven, untreated locoregionally advanced nasopharyngeal carcinoma (LANPC) at high-risk of distant metastasis (T4N1 and T1-4N2-3, according to American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC] 8th edition clinical staging system). Patients will receive 3 cycles of induction chemotherapy (IC; gemcitabine-cisplatin regimen) followed by intensity-modulated radiotherapy (IMRT) alone. Nivolumab injection OPDIVO® will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. The first and last 3 cycles of nivolumab are administrated concurrently with IC and IMRT, respectively. After 4 weeks of the completion of IMRT, adjuvant nivolumab will begin every 4 weeks for 6 cycles.

Study Type

Interventional

Enrollment (Estimated)

152

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 Locations

  • China
    • Fujian Provinve
      • Fuzhou, Fujian Provinve, China
        • Fujian Provinve Cancer Hospital
    • Guizhou
      • Guiyang, Guizhou, China
        • Cancer Hospital of Guizhou Medical University
    • Hubei
      • Wuhan, Hubei, China
        • Hubei Province Cancer Hosiptal
      • Wuhan, Hubei, China
        • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
    • Hunan
      • Changsha, Hunan, China
        • Xiangya Hospital Central South University
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Zhejiang Province Cancer Hospital

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. Age: 18 to 65;
  2. Pathological type: non-keratinizing carcinoma (World Health Organization criteria);
  3. Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC];
  4. ECOG performance score: 0 to 1;
  5. Normal bone marrow function: white blood cell count > 4×109/L, hemoglobin > 90g/L, platelet count > 100×109/L;
  6. Normal values of thyroid function, amylase and lipase examination, pituitary function, inflammation and infection indicators, myocardial enzymes, and ECG results. For patients older than 50 years with a smoking history, normal lung function are required. Patients with abnormal ECG and/or a history of vascular disease (but not meeting the exclusion criteria listed in the exclusion criteria 7) need further testing and require normal results of myocardial function and color Doppler ultrasound.
  7. Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine transaminase and aspartate transaminase ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; creatinine clearance rate ≥ 60 ml/min;
  8. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
  9. Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.

Exclusion Criteria:

  1. Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA > 1×10E3 copies/ml; anti-hepatitis C virus positive;
  2. Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
  3. Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment; history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
  4. Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
  5. Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
  6. Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
  7. Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2); 2) unstable angina; 3) myocardial infarction in past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
  8. Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
  9. Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
  10. Allergy to macromolecular protein preparations, or any component of nivolumab;
  11. Active infection requiring systemic treatment;
  12. Receiving live vaccine within 30 days of the initial nivolumab;
  13. History of organ transplantation;
  14. History of psychotropic disease, alcoholism or drug abuse; other situation assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PD-1 blocking antibody combined with IC+IMRT
All participants will receive induction chemotherapy (IC; every 3 weeks × 3 cycles; gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1) followed by intensity-modulated radiotherapy (IMRT; 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day) alone. PD-1 blocking antibody (360 mg per cycle) will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. The first and last 3 cycles of PD-1 blocking antibody are administrated concurrently with IC and IMRT, respectively. After 4 weeks of the completion of IMRT, adjuvant PD-1 blocking antibody (480 mg per cycle) will begin every 4 weeks for 6 cycles.
Radiation: Intensity-modulated radiotherapy
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Other Names:
  • IMRT
Drug: PD-1 blocking antibody
  1. Whole-course concurrent PD-1 blocking antibody: every 3 weeks × 6 cycles; 360 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone.
  2. Adjuvant PD-1 blocking antibody: every 4 weeks × 6 cycles; 480 mg, day 1
Other Names:
  • PD-1 blockade
Drug: Gemcitabine
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles
Other Names:
  • GEM
Drug: Cisplatin
Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles
Other Names:
  • DDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure-free survival (FFS)
Time Frame: 3-year
Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first
3-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 3-year
Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive
3-year
Distant failure-free survival (DFFS)
Time Frame: 3-year
Distant failure-free survival is measured from day of diagnosis until distant metastasis
3-year
Incidence rate of investigator-reported adverse events (AEs)
Time Frame: 3-year
Analysis of investigator-reported 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
3-year
Incidence rate of patient-reported adverse events (AEs)
Time Frame: 3-year
Analysis of patient-reported 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 patients themselves
3-year
Locoregional failure-free survival (LRFFS)
Time Frame: 3-year
Locoregional failure-free survival is measured from day of diagnosis until local or regional recurrence
3-year
Quality of life (QoL): questionnaire
Time Frame: week 1, 20, 40, 64
Changes in QoL of participants from initial treatment to 6 months after the completion of 6 cycles adjuvant PD-1 blocking antibody. QoL is evaluated with the use of (1) the head-and-neck-specific module (H&N35) of the Quality of Life Questionnaire-Core 30 module (QLQ-C30), which is established by European Organization for Research and Treatment of Cancer (EORTC) and (2) the general and head-and-neck-specific module of the evaluation tool developed by the Functional Assessment of Cancer Therapy (FACT). Scores for the module range of H&N35 QLQ-C30 from 0 to 100, with higher scores indicating better functioning or well-being or higher symptom burden (scales measuring symptom burden were reverse-scored to facilitate presentation)
week 1, 20, 40, 64

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between pre-treatment PD-L1 expression level and FFS
Time Frame: 3-year
Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative.
3-year
Correlation between pre-treatment PD-L1 expression level and OS
Time Frame: 3-year
Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative.
3-year
Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS
Time Frame: 3-year
TILs are lymphoid cells (T cells) that infiltrate solid tumors (intra-tumoral TILs) and stroma (stromal TILs), which play an important role in the tumor microenvironment. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative.
3-year
Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and OS
Time Frame: 3-year
TILs are lymphoid cells (T cells) that infiltrate solid tumors (intra-tumoral TILs) and stroma (stromal TILs), which play an important role in the tumor microenvironment. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative.
3-year
Evaluate failure-free survival in the subgroup of age at diagnosis (year)
Time Frame: 3-year
Subgroup analysis
3-year
Evaluate failure-free survival in the subgroup of gender (male and female)
Time Frame: 3-year
Subgroup analysis
3-year
Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level
Time Frame: 3-year
Subgroup analysis
3-year
Evaluate failure-free survival in the subgroup of clinical stage
Time Frame: 3-year
Subgroup analysis
3-year

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Collaborators

Bristol-Myers Squibb

Investigators

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

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)

March 16, 2020

Primary Completion (Estimated)

March 30, 2024

Study Completion (Estimated)

March 30, 2024

Study Registration Dates

First Submitted

June 7, 2019

First Submitted That Met QC Criteria

June 11, 2019

First Posted (Actual)

June 13, 2019

Study Record Updates

Last Update Posted (Estimated)

February 6, 2024

Last Update Submitted That Met QC Criteria

February 3, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-7GC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We currently have no plans to share individual participant data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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