The Efficacy and Safety of Sintilimab in Combination With Multimodal Radiotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

The Efficacy and Safety of Sintilimab in Combination With Multimodal Radiotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma After Multi-line Treatment (Including Immunotherapy)

Nasopharyngeal carcinoma is the most common malignant tumor of head and neck in southern China. After standard treatment, about 20% of the patients had local recurrence or distant metastasis, and the patients faced death in a short time. Currently, there is no recommended treatment for patients with recurrent or metastatic nasopharyngeal carcinoma who have unsatisfactory results of first-line chemotherapy and subsequent immunotherapy. Patients who have failed multiline therapy have a low survival rate and no drugs are available.This project aims to evaluate the efficacy and safety of sintilimab in combination with multimodal radiotherapy for patients with recurrent or metastatic nasopharyngeal carcinoma who have previously received immunotherapy and still progress after multiline therapy, and to seek a new therapeutic approach for such patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Sintilimab in combination with Multimodality Radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xingchen Peng, Ph.D; Phone Number: 18980606753; Email: pxx2014@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The histopathological diagnosis was recurrent or distant metastatic nasopharyngeal carcinoma;
2. Have received two or more lines of treatment, including at least one immunocheckpoint inhibitor related therapy containing PD-1/L1, and have achieved clinical benefit;
3. Aged between 18 and 65 at the date of signing the informed consent;
4. ECOG score 0-1;
5. At least ≥1 measurable lesion according to Recist v1.1, or ≥1 measurable lesion with definite progression after local treatment (based on Recist v1.1 criteria);At the same time, there were more than 1 radiotherapy foci and lesions with radiographic evaluation of distant effect.
6. Life expectancy ≥12 weeks;
7. Major organ functions within 28 days prior to treatment meet the following criteria:

A. Routine blood test criteria (without blood transfusion within 14 days) : hemoglobin (Hb) ≥80g/L;Neutrophils absolute value (ANC) ≥1.5×109/L;Platelet (PLT) ≥80×109/L; B. Biochemical tests should meet the following criteria: total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, if accompanied by liver metastasis, ALT and AST≤5×ULN;Serum creatinine (CR) ≤1.5×ULN or creatinine clearance rate (CCR)≥60ml/min; C. Coagulograms should meet the following criteria: International Standardized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5ULN;Activated partial thromboplastin time (APTT) ≤1.5 ULN (if the patient is receiving anticoagulant therapy, as long as PT and APTT are within the expected treatment range); D. centrifuge markers and urinary natriuretic peptide (BNP) ≤ULN; E. Thyroid function: T3 and T4 levels were normal after medication; 8. Women of reproductive age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and for 120 days after the end of the study;Negative serum or urinary pregnancy test within 7 days prior to study enrollment; 9. With my consent and signed the informed consent.

Exclusion Criteria:

1. Previous use of immunocheckpoint inhibitors combined with radiotherapy after recurrence and metastasis;
2. A history of other malignant tumors within the previous 5 years or at the same time, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix and papillary carcinoma of the thyroid;
3. known allergic reactions to active ingredients of PD-1 monoclonal antibody or any excipients;
4. Symptomatic central nervous system metastasis;
5. Those who had received potent CYP3A4 inhibitor treatment within one week before enrollment, or inducer CYP3A4 treatment within two weeks before enrollment;
6. The New York Heart Association's cardiac function classification is Grade III-IV congestive heart failure;
7. An ischemic cardiovascular event occurred within 1 year prior to treatment;
8. QT interval of ECG >500 ms;
9. Have received systemic immunosuppressive therapy;
10. Participate in clinical trials of other interventional drugs within 4 weeks before the first administration;
11. Subjects who require systematic treatment with corticosteroids (greater than 10mg equivalent daily dose of prednisone) or other immunosuppressant within 2 weeks prior to the first use of the study drug;
12. Have received an anti-tumor vaccine or a live vaccine within 4 weeks before the first administration of the investigational drug;
13. Major surgery or severe trauma within 4 weeks before the first use of the study drug;
14. Severe infections (CTCAE > grade 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, infection complications, etc., requiring hospitalization;Baseline chest imaging examination suggests active pulmonary inflammation, signs and symptoms of infection within 2 weeks prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment (excluding prophylactic use of antibiotics);
15. Have a history of active autoimmune diseases or autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes);Autoimmune-mediated hypothyroidism treated with a steady dose of thyroid-replacement hormone and with a steady dose of insulin in type 1 diabetes were included;This does not include patients with vitiligo or cured childhood asthma/allergies who do not need any intervention as adults;
16. Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or bone marrow transplantation;
17. History of non-infectious pneumonia
18. Patients with active tuberculosis infection found by medical history or CT examination, or patients with active tuberculosis infection found within 1 year before enrollment, or patients with active tuberculosis infection found before 1 year but without formal treatment;
19. Subsubjects had active hepatitis (HBV DNA≥2000IU/ mL or 10000 copies/ mL) and hepatitis C (HCV antibody positive and HCV-RNA above the detection limit of the assay method);
20. A history of known abuse of psychotropic substances, alcoholism and drug abuse;
21. Being pregnant or lactating;
22. There is any history, disease, treatment, or abnormal laboratory result that may interfere with the results of the study and prevent subjects from participating fully in the study, or the investigator deems that participation is not in the best interest of the subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Sintilimab in combination with Multimodality Radiotherapy group; The dose of sintilimab was 200mg per dose, intravenously, once every 3 weeks. Multimodal radiotherapy methods: ①SBRT: ≥1 independent lesion was selected, with a single dose of 8-10Gy and a total dose of 40-60Gy, divided into 5-6 times of radiotherapy. The final frequency and total dose of radiotherapy were determined by the radiologist.② Low-dose radiotherapy: ≥1 independent lesion was selected, and the single dose, the final frequency of radiotherapy and the total dose were determined by the radiologist.

Drug: Sintilimab in combination with Multimodality Radiotherapy; Participants will be treated with sintilimab in combination with multimodality radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	up to approximately 2 years
Overall survival	up to approximately 2 years
Duration of remission	up to approximately 2 years
1 year overall survival	1 years after treatment finished
Adverse reactions	Time Frame: from the first drug administration to within 30 days for the last therapy

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: Sichuan Provincial People's Hospital; The First People's Hospital of Ziyang; Chengdu City No.2 People's Hospital; No.3 People's Hospital of Chengdu; No.5 People's Hospital of Chengdu

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 30, 2021
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): June 30, 2024

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (ACTUAL): June 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Sintilimab; nasopharyngeal carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: HX20210601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No