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

Nasopharyngeal Neoplasms Clinical Trial

Official title:

Neoadjuvant Sintilimab (PD-1 Antibody)-Chemotherapy and Concurrent Sintilimab-chemoradiation in Locoregionally-advanced Nasopharyngeal Carcinoma: a Single-arm, Phase 2 Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03619824
• Other study ID #: B2018-090-01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 2019
• Est. completion date: March 2024

Study information

• Verified date: October 2018
• Source: Sun Yat-sen University
• Contact: Jun Ma
• Phone: +862087343469
• Email: majun2[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: March 2024
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nasopharyngeal Neoplasms

Intervention

Drug:
• Sintilimab
Sintilimab 200mg ivdrip, every 3 weeks for 6 cycles
• Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
• Cisplatin
Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

Radiation:
• intensity-modulated radiotherapy
Definitive IMRT of 66-70Gy will be given in six to seven weeks.

Locations

Country	Name	City	State
China	SUN YAT-SEN UNIVERSITY cANCER CENTER	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	The proportion of patients who completed radiation within 8 weeks		8 weeks
Secondary	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.
Secondary	Failure-free survival	calculated from the date of informed consent to the date of locoregional failure, distant failure, or death from any cause, whichever occurred first.	3 years
Secondary	Overall survival	calculated from the date of informed consent to the date of death from any cause.	3 years
Secondary	Distant failure-free survival	calculated from the date of informed consent to the date of distant metastasis.	3 years
Secondary	Locoregional failure-free survival	calculated from the date of informed consent to the the date of locoregional persistence or 1st locoregional recurrence.	3 years