Sintilimab Combination Therapy Plus IMRT in Nasopharyngeal Carcinoma

Gemcitabine, Sintilimab, Bevacizumab Plus IMRT in Patients With Cisplatin Ineligible Locoregionally Advanced Nasopharyngeal Carcinoma

This is a prospective, single-center, single-arm, phase II clinical study. The study was intended to include patients with locoregionally advanced nasopharyngeal cancer identified by histology or cytology, who signed informed consent and met the screening criteria to enter the study. Patients will receive induction therapy (sintilimab + bevacizumab + gemcitabine, Q3W, 3 cycles) followed by IMRT+ Sintilimab. Consolidation therapy with sintilimab continued after radiotherapy until disease progression, intolerable toxicity, death, or the subject's decision to withdraw from the study, with a total treatment period of no more than 12 cycles.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Sintilimab, bevacizumab, gemcitabine; Radiation: IMRT

Detailed Description

Platinum deplatinization has been extensively explored in patients with posterior nasopharyngeal carcinoma who have received multiple platinum treatments, including target-free combination, GEP, etc. Our center also published in 2022 CSCO a study on the preliminary efficacy of pembrolizumab combined with gemcitabine in the first-line treatment of metastatic NPC with or without cisplatin or anlotinib. Enrolled patients were treated with pembrolizumab + anlotinib +GP (group A), pembrolizumab +GP (group B), and pembrolizumab + anlotinib +G (group C), with ORR of 80% (4/5), 80% (4/5), and 100% (7/7), respectively. Among them, there were 1 CR and 6 PR in group C. Compared to group B, group C with anlotinib in place of cisplatin showed a better safety profile with fewer grade 3 adverse reactions (57.1% vs 100%). In summary, we designed this study to evaluate the efficacy and safety of gemcitabine, sintilimab and bevacizumab combined with IMRT in patients with advanced nasopharyngeal carcinoma not suitable for platinum-based treatment, and to explore new therapeutic approaches for patients with advanced stage nasopharyngeal carcinoma who cannot tolerate platinum therapy or are unwilling to receive platinum therapy.

This is a prospective, single-center, single-arm, phase II clinical study. The study was intended to include patients with locoregionally advanced nasopharyngeal cancer identified by histology or cytology, who signed informed consent and met the screening criteria to enter the study. Patients will receive induction therapy (sintilimab + bevacizumab + gemcitabine, Q3W, 3 cycles) followed by IMRT+ Sintilimab. Consolidation therapy with sintilimab continued after radiotherapy until disease progression, intolerable toxicity, death, or the subject's decision to withdraw from the study, with a total treatment period of no more than 12 cycles.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Sign a written informed consent before implementing any procedures related to the trial; 2. No gender limitation, age ≥18 years old, ≤75 years old; 3. Histological or cytological determination of advanced nasopharyngeal carcinoma assessed by the investigator without any treatment (stage III-IVA, except T3N0M0); 4. Not suitable for platinum therapy (patients > 70 years old, PS > 2, hearing impairment, renal insufficiency (creatinine clearance < 50ml/min) or grade 1 neuropathy;2023 CSCO Guidelines for the Diagnosis and Treatment of Head and Neck Tumors) or patients do not receive platinum therapy; 5. The ECOG PS score is 0-1; 6. According to the solid tumor efficacy evaluation criteria (RECIST version 1.1), there is at least one radiographically measurable lesion; 7. Expected survival time > 6 months; 8. Adequate organ function.

Exclusion Criteria:

• 1. Patients with uncured malignancies other than advanced nasopharyngeal carcinoma diagnosed within 5 years prior to initial administration (excluding radical basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical resection); 2. Is currently participating in an interventional clinical study, or has received other investigational drugs or used investigational devices within 4 weeks prior to initial dosing; 3. Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that target another stimulus or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137); 4. Previously received anti-angiogenic therapy, including but not limited to anti-angiogenic monoclonal antibodies, anti-angiogenic TKI, etc.; 5. Received systemic systemic treatment with proprietary Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin) within 2 weeks before the first administration; 6. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to first administration.Replacement therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy; 7. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 8. Known active ingredients or excipients of Sintilimab and bevacizumab in this study, and allergic patients to chemotherapy drugs in this study; 9. Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss); 10. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 11. Other researchers did not consider it appropriate to study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sintilimab, bevacizumab, gemcitabine; Patients will receive induction therapy (sintilimab + bevacizumab + gemcitabine, Q3W, 3 cycles) followed by IMRT+ Sintilimab. Consolidation therapy with sintilimab continued after radiotherapy until disease progression, intolerable toxicity, death, or the subject's decision to withdraw from the study, with a total treatment period of no more than 12 cycles.

Drug: Sintilimab, bevacizumab, gemcitabine; This is a prospective, single-center, single-arm, phase II clinical study. The study was intended to include patients with locoregionally advanced nasopharyngeal cancer identified by histology or cytology, who signed informed consent and met the screening criteria to enter the study. Patients will receive induction therapy (sintilimab + bevacizumab + gemcitabine, Q3W, 3 cycles) followed by IMRT+ Sintilimab. Consolidation therapy with sintilimab continued after radiotherapy until disease progression, intolerable toxicity, death, or the subject's decision to withdraw from the study, with a total treatment period of no more than 12 cycles.; Radiation: IMRT; IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Event-free survival rate	The time between the start of treatment and the first occurrence of any of the following events: disease progression, local or distant recurrence, death from any cause, whichever occurs first	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Proportion of total subjects in complete response (CR) and partial response (PR)	3 years
Disease Control Rate	Proportion of subjects defined as complete response (CR), partial response (PR), and stable disease (SD)	3 years
Progression-Free Survival	The time between the start of treatment and first radiographic disease progression or death, whichever occurs first	3 years
Overall survival	The time of treatment until the subject dies from any cause	3 years
adverse events(AEs)	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarkers	To evaluate the relationship between biomarkers and response	3 years

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 22, 2024
• Primary Completion (Estimated): April 22, 2026
• Study Completion (Estimated): April 22, 2026

Study Registration Dates

• First Submitted: March 26, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: bevacizumab; IMRT; sintilimab; locoregionally advanced 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Gemcitabine
• Other Study ID Numbers: NPC-202403

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
• product manufactured in and exported from the U.S.: No