Clinical trial NCT03619824: PD-1 Blockade Combined With Definitive Chemoradiation in Locoregionally-advanced Nasopharyngeal Carcinoma
Official title: Neoadjuvant Sintilimab (PD-1 Antibody)-Chemotherapy and Concurrent Sintilimab-chemoradiation in Locoregionally-advanced Nasopharyngeal Carcinoma: a Single-arm, Phase 2 Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Nasopharyngeal Neoplasms
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Innovent Biologics (Suzhou) Co. Ltd.
First posted: 2018-08-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial plans to enroll 40 patients with stage III-IVA (AJCC 8th, except T3N0-1 or T4N0) locoregionally-advanced nasopharyngeal carcinoma (NPC). Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation. All patients will receive intensity-modulated radiotherapy (IMRT). Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 6 cycles.


Eligibility criteria: Inclusion Criteria:

1. Patients with histologically confirmed nasopharyngeal carcinoma.
2. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
3. ECOG 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 HBV DNA \>1×10e3 copies/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 a known history of interstitial lung disease.
6. 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.
7. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
8. Is pregnant or breastfeeding.
9. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
10. Has known allergy to large molecule protein products or any compound of sintilimab.
11. Has a known history of human immunodeficiency virus (HIV) infection.
12. 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.

Primary outcomes:
measure: Immune-related adverse events (irAEs) and serious adverse events (irSAEs)
timeFrame: From the date of informed consent to 100 days after treatment
measure: All adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From the date of informed consent to 100 days after treatment
Secondary outcomes:
measure: The proportion of patients who completed radiation within 8 weeks
timeFrame: 8 weeks
measure: The proportion of patients who completed 6 cycles of sintilimab
timeFrame: From the date of informed consent to the end of treatment, assessed up to 20 weeks.
measure: Failure-free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Distant failure-free survival
timeFrame: 3 years
measure: Locoregional failure-free survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: SUN YAT-SEN UNIVERSITY cANCER CENTER
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Jun Ma
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li XM, Zhang XM, Li JY, Jiang N, Chen L, Tang LL, Mao YP, Li WF, Zhou GQ, Li YQ, Liu N, Zhang Y, Ma J. The immune modulation effects of gemcitabine plus cisplatin induction chemotherapy in nasopharyngeal carcinoma. Cancer Med. 2022 Sep;11(18):3437-3444. doi: 10.1002/cam4.4705. Epub 2022 Mar 30.