Nivolumab Combined With Chemoradiotherapy Sparing Concurrent Cisplatin in Nasopharyngeal Carcinoma

NCT ID: NCT03984357

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-16
• Study Completion Date: 2025-03-30

Brief Summary

This is a phase 2, single-arm, multicenter clinical trial, with the purpose to evaluate the therapeutic efficacy, safety, and tolerability of PD-1 Blockade nivolumab combined with a deintensified chemoradiotherapy by sparing concurrent cisplatin from the standard induction chemotherapy plus concurrent chemoradiotherapy in high-risk locoregionally advanced nasopharyngeal carcinoma.

Detailed Description

This phase 2, single-arm, multicenter clinical trial plans to enroll 152 patients with newly-diagnosed, pathologically-proven, untreated locoregionally advanced nasopharyngeal carcinoma (LANPC) at high-risk of distant metastasis (T4N1M0 or T1-4N2-3M0, 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 the completion of IMRT, adjuvant nivolumab will begin every 4 weeks for 6 cycles.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PD-1 blocking antibody

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles

Cisplatin

Intervention Type: DRUG

Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles

Intensity-modulated radiotherapy

Intervention Type: RADIATION

Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day

Interventions

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

Intervention Type: DRUG

Gemcitabine

Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles

Intervention Type: DRUG

Cisplatin

Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles

Intervention Type: DRUG

Intensity-modulated radiotherapy

Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day

Intervention Type: RADIATION

Other Intervention Names

PD-1 blockade; GEM; DDP; IMRT

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;

Exclusion Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Jun Ma, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Ma, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Fujian Provinve Cancer Hospital

Fuzhou, Fujian Provinve, China

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Xiangya Hospital Central South University

Changsha, Hunan, China

Zhejiang Province Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

References

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Other Identifiers

CA209-7GC

Identifier Type: -

Identifier Source: org_study_id