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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Failure-free survival (FFS)

Secondary Outcome

 Overall survival (OS)

Condition

Nasopharyngeal Carcinoma

Intervention

PD-1 blocking antibody

Study Arms / Comparison Groups

 PD-1 blocking antibody combined with IC+IMRT

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

152

Start Date

March 16, 2020

Completion Date

August 2026

Primary Completion Date

August 2024

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Jun Ma, M.D., +862087343469, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT03984357

Organization ID

CA209-7GC

Responsible Party

Principal Investigator

Study Sponsor

Sun Yat-sen University

Collaborators

 Bristol-Myers Squibb

Study Sponsor

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

Verification Date

December 2020