GEP Combined With Radiotherapy in Non-locally Treatable Recurrent NPC

A Prospective, Single-arm Phase II Clinical Study of GEP (Gemcitabine, Recombinant Human Endostatin, and Carrellizumab) Combined With High-low-dose Radiotherapy in Non-locally Treatable Recurrent Nasopharyngeal Carcinoma

This research aims to assess both effectiveness and safety of combining R-GEP regimen comprising gemcitabine, recombinant human endostatin, and cerexinib with low- and high-dose radiotherapy in managing unresectable recurrent nasopharyngeal carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharynx Cancer
• Intervention / Treatment: Drug: GEP (Gemcitabine, Recombinant Human Endostatin, and Carrellizumab) Combined With High-low-dose Radiotherapy

Detailed Description

Eligible patients will undergo screening before enrolling in this trial 。 The participants will receive R-GEP therapy according to specified dosing schedules over six cycles. Additionally administered low-dose radiotherapy during specific cycles serves to modulate immune microenvironment while high-dose fractionated radiotherapy follows completion of GEP therapy courses. Maintenance immunotherapy continues up until one year post-treatment conclusion or disease progression.Finally, the participants were evaluated accordingly。

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huang shuang; Phone Number: 18258111085; Email: hnhuangshuang525@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged ≥18 years;
2. ECOG performance status 0-2;
3. Pathological or clinical imaging diagnosis of recurrent nasopharyngeal carcinoma;
4. With imaging assessable lesions (assessed by RECIST 1.1 criteria);
5. Recurrent lesions are not eligible for curative local treatment (including but not limited to extensive invasion of recurrent lesions; recurrent lesions with obvious necrosis or ulceration, with bleeding risk; recurrent lesions extensively invading surrounding nerves/vessels or skin/muscle; obvious late radiation therapy complications after previous treatment: radiation-induced brain injury, posterior cranial nerve injury, dysphagia, severe myofibrosis; second or multiple courses of radiation therapy after recurrence or multiple recurrences);

6. The following requirements must be met for the function of major organs:

   Hematological parameters tolerable to treatment: white blood cells ≥3.0×10^9/L, neutrophils ≥1.5×10^9/L, hemoglobin ≥9 g/dL, platelets ≥90×10^9/L.

   Liver and kidney function: ALT, AST <1.5 times the upper limit of normal (ULN), total bilirubin <1.5×ULN, serum creatinine (Cr) ≤1.5×ULN; Echocardiographic assessment, left ventricular EF ≥50%;

7. The patient has signed an informed consent form and is willing and able to comply with the visit schedule, treatment plan, laboratory tests, and other research procedures.
8. Voluntarily enroll in this study, sign an informed consent form, have good compliance and willingness to cooperate with follow-up.

Exclusion Criteria:

1. Subjects who cannot accept or tolerate chemotherapy or radiotherapy for various reasons;
2. Subjects who can be cured by definitive radiotherapy or surgery;
3. Subjects who have undergone major surgical procedures within the past 4 weeks or have not fully recovered from such procedures;
4. Subjects who are currently participating in other drug clinical trials;

5. Serious cardiac disease or discomfort, including but not limited to the following conditions:

   • History of congestive heart failure or impaired systolic function (LVEF <50%);
   • Uncontrolled high-risk arrhythmias, such as atrial tachycardia, resting heart rate >100bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-level atrioventricular conduction block (i.e., Mobitz Ⅱ second-degree atrioventricular conduction block or third-degree atrioventricular conduction block);
   • Angina requiring anti-angina drug therapy;
   • Clinically significant valvular heart disease;
   • ECG showing a penetrating myocardial infarction;
   • Uncontrolled hypertension (systolic blood pressure >180mmHg and/or diastolic blood pressure >100mmHg);
6. Subjects who have a history of hypersensitivity to any component of the study drug;
7. Any other situation in which the investigator deems the subject unsuitable to participate in the study.

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: GEP; Gemcitabine, recombinant human endostatin and carrilizumab combined with high-low dose radiotherapy

Drug: GEP (Gemcitabine, Recombinant Human Endostatin, and Carrellizumab) Combined With High-low-dose Radiotherapy; The R-GEP regimen is as follows: Gemcitabine (G; 1.0 g/m2, d1, d8) in combination with recombinant human vascular endothelial growth factor (E; 150 mg, continuous intravenous infusion for 72 hours) and Carelizumab (P; 200 mg), administered every three weeks for a total of six cycles. During the 2nd-4th cycles, low-dose radiotherapy is administered to modulate the immune microenvironment (R: one course of radiotherapy per cycle: including booster fractions of 1 Gy*3 times for the recurrent lesions, once a day, for three cycles). Approximately three weeks after the completion of the sixth cycle of GEP regimen (or the last cycle), high-dose fractionated radiotherapy (5-8 Gy*5 times, once a day) is given to the recurrent lesions. Immune maintenance therapy continues until one year after treatment completion or disease progression.; Other Names: recombinant human endostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year OS rate	3 year OS rate	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR	3year
DCR	DCR	3year
3 year PFS rate	3 year PFS rate	3 year

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Endostatins; Gemcitabine
• Other Study ID Numbers: IRB-2024-766（IIT）

Drug and device information, study documents

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