PD-1 Blockade Combined With Definitive Chemoradiation in Locoregionally-advanced Nasopharyngeal Carcinoma

NCT03619824 | Unknown Phase 2 DMC

• 1 other identifier: B2018-090-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Neoplasms

Outcome Measures

Primary Outcomes (2)

• Immune-related adverse events (irAEs) and serious adverse events (irSAEs)

  Graded according to CTCAE V5.0

  From the date of informed consent to 100 days after treatment

• All adverse events (AEs) and serious adverse events (SAEs)

  Graded according to CTCAE V5.0

  From the date of informed consent to 100 days after treatment

Secondary Outcomes (6)

• The proportion of patients who completed radiation within 8 weeks

  8 weeks

• The proportion of patients who completed 6 cycles of sintilimab

  From the date of informed consent to the end of treatment, assessed up to 20 weeks.

• Failure-free survival

  3 years

• Overall survival

  3 years

• Distant failure-free survival

  3 years

Study Arms (1)

Intervention arm

EXPERIMENTAL

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 66-70Gy will be given in six to seven weeks. Concurrent cisplatin 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Sintilimab 200mg will be given every 3 weeks for 6 cycles, started on day 1 of induction chemotherapy.

Drug: Sintilimab; Drug: Gemcitabine; Drug: Cisplatin; Radiation: intensity-modulated radiotherapy

Interventions

Sintilimab DRUG

Sintilimab 200mg ivdrip, every 3 weeks for 6 cycles

Also known as: IBI308, PD-1 antibody

Intervention arm

Gemcitabine DRUG

Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.

Intervention arm

Cisplatin DRUG

Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

Also known as: DDP

Intervention arm

intensity-modulated radiotherapy RADIATION

Definitive IMRT of 66-70Gy will be given in six to seven weeks.

Also known as: IMRT

Intervention arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed nasopharyngeal carcinoma.
• Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
• ECOG performance status ≤1.
• Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
• Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
• Patients must be informed of the investigational nature of this study and give written informed consent.
• 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.

You may not qualify if:

• Age \> 65 or \< 18.
• Hepatitis B surface antigen (HBsAg) positive and HBV DNA \>1×10e3 copies/ml
• Hepatitis C virus (HCV) antibody positive
• 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).
• Has a known history of interstitial lung disease.
• 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.
• Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
• Is pregnant or breastfeeding.
• Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
• Has known allergy to large molecule protein products or any compound of sintilimab.
• Has a known history of human immunodeficiency virus (HIV) infection.
• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

SUN YAT-SEN UNIVERSITY cANCER CENTER

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• 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.

  PMID: 35355438 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

sintilimab; spartalizumab; Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Jun Ma

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Ma

CONTACT

+862087343469; majun2@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 8, 2018
• Study Start: January 1, 2019
• Primary Completion: October 1, 2019
• Study Completion: March 1, 2024
• Last Updated: October 9, 2018

Record last verified: 2018-10

Locations

CN (1)