Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma

Predictive-Model Based Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma: A Phase 2 Randomized Trial

This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized carbon-ion radiotherapy (CIRT). For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Recurrent Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: Standardized CIRT; Radiation: Individualized CIRT

Detailed Description

This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized CIRT with a dose of 63 gray equivalent (GyE) in 21 fractions (fx). This regimen was obtained from our previous phase 1 (dose escalation) study. For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups. The secondary endpoints include 2-year overall survival (OS), local progression-free survival, regional progression-free survival, distant metastasis-free survival, toxicities and quality of life.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lin Kong, MD; Phone Number: +8602138296666-53516; Email: lin.kong@sphic.org.cn
• Study Contact Backup: Name: Jiyi Hu, MD, PhD; Phone Number: +8602138296666-53516; Email: jiyi.hu@sphic.org.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201315
      • Shanghai Proton and Heavy Ion Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged between 17-70 years.
• Pathologically diagnosed as WHO type 2/3 nasopharyngeal carcinoma.
• Failed previous definitive radiotherapy at least 6 months ago.
• Only had 1 previous course of radiotherapy.
• Eastern Cooperative Oncology Group score: 0-1.
• Adequate laboratory values within 30 dyas of enrollment to study defined as follows: 1) neutrophil > 2000/mm^3; 2) platelet > 100,000/mm^3; 3) total bilirubin < 1.5mg/dl; 4) alanine aminotransferase/aspartate aminotransferase < 1.5 upper limit of normal; 5) SCr < 1.5mg/dl; creatinine clearance rate > 60ml/min.
• Willing to accept adequate contraception for women with childbearing potential.
• Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial.

Exclusion Criteria:

• Presence of distant metastasis.
• Without measurable lesion.
• Previous history of malignant tumor (within 5 years) or simultaneous existence of multiple primary tumors.
• Accompanied with severe major organ dysfunction.
• Presence of mental disease that may influence the understanding of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standardized CIRT; Patients will receive standardized CIRT with a dose of 63 GyE/21 fx.	Radiation: Standardized CIRT; CIRT with a dose of 63 GyE/21 fx
Experimental: Individualized CIRT; A previously predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively.	Radiation: Individualized CIRT; A predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	From randomization to death or disease progression, a median of 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	From randomization to death, a median of 2 years
Local progression-free survival	From randomization to local failure, a median of 2 years
Regional progression-free survival	From randomization to regional failure, a median of 2 years
Distant metastasis-free survival	From randomization to distant metastasis, a median of 2 years
Incidence of radiation-induced acute toxicity evaluated by CTCAE 5.0	Within 3 months after initiation of radiation therapy
Incidence of radiation-induced late toxicity evaluated by CTCAE 5.0	Three months after initiation of radiation therapy
Quality of life by questionnaires evaluated using EORTC-Q30 questionnaire.	Throughout the study, an average of 2 years
Quality of life by questionnaires evaluated using EORTC-H&N35 questionnaire.	Throughout the study, an average of 2 years

Collaborators and Investigators

• Sponsor: Shanghai Proton and Heavy Ion Center

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): September 30, 2025

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Survival; Toxicity; Locally recurrent nasopharyngeal carcinoma; Individualized carbon-ion radiotherapy; Predictive model of mucosal necrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Recurrence
• Other Study ID Numbers: SPHIC-TR-HNCNS-2020-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data including baseline characteristics, treatment information and follow-up data on toxicity, survival and disease control will be shared.
• IPD Sharing Time Frame: Within 5 years after the publication of the study.
• IPD Sharing Access Criteria: Data may be shared with radiation oncologists who are interested in examining the efficacy and toxicity of locally recurrent nasopharyngeal carcinoma patients treated with particle beam radiotherapy. Detailed study protocol should be emailed along with the request of the data. We may carefully review the study protocol, and data will only be shared with well-designed studies.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

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