NSCLC Isotoxic Hypofractionated Radiotherapy (IHR)

A Phase II Open-Label Multi-center Trial of Isotoxic Hypofractionated Radiotherapy for NSCLC

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the over treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher biological effective dose（BED）.So far, the vast majority of radiotherapy prescriptions have given a uniform dose of 60 Gy. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as possible. We will integrate this concept with hypofractionated radiotherapy in order to further improve patient survival.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Radiation: isotoxic hypofractionation

Detailed Description

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the over treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher biological effective dose（BED） So far, the vast majority of radiotherapy prescriptions have given a uniform dose of radiotherapy to all patients, regardless of individual factors such as tumor size, location, and adjacent vital organs, which may cause two consequences: First, small-volume tumors may, not receive enough radiation dose, resulting in a decrease in local control rates. Second, for large volumes of tumors or tumors adjacent to vital organs, even the "so-called standard dose" (60 Gy) may cause serious damage to normal tissues. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., and each patient receives a different dose of radiation therapy. This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as .From the model study to the long-term survival results, a series of encouraging results were achieved. The use of an individualized radiotherapy prescription based on iso-toxicity for the treatment of NSCLC in large-segment radiotherapy is expected to achieve: 1. For patients with small tumor volumes and no adjacent to vital organs, a higher radiation dose is given under safe conditions. 2. For patients with larger volumes of tumors or adjacent to vital organs, give safer doses.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiao-Ying Xue, Professor; Phone Number: +86-158-0321-0636; Email: xxy0636@163.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Second Hospital of Hebei Medical University
      • Contact: Xiao-Ying Xue, Professor; Phone Number: +86-158-0321-0636; Email: xxy0636@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Pathological or cytological diagnosis of non-small cell lung cancer patients, the clinical stage using the eighth edition of American Joint Committee on Cancer（AJCC）, including stage III without resectable or who when SBRT/SABR are not suitable;
2. Age ≥ 18 years;
3. The expected survival period is ≥ 3 months;
4. KPS score ≥ 60;
5. Normal blood count,liver and kidney function ≤ 2.5 times the upper limit of normal;

Exclusion Criteria:

1. Serious medical problems require hospitalization, included (but not limited to ): history of pulmonary fibrosis, previous myocardial infarction within 6 months, heart failure grade II and above, uncontrolled heart failure, uncontrolled COPD, uncontrolled diabetes Wait;
2. Esophageal invasion (cT4);
3. Others are not suitable for receiving radiotherapy.

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: isotoxic hypofractionation group; 1. Hypofractionated radiation: 3Gy/f. 2,Individualized prescriptions for different patients: (1) Spinal cord: 0%>45 Gy, and ≤2 Gy each time Lung: V20≤30%, V5≤65%, MLD≤16Gy Esophagus: highest dose ≤ 72Gy 3. Maximum limit: If the limit of any "A" is not reached, the maximum radiation dose is 72 Gy. The lowest radiation dose: 45Gy.	Radiation: isotoxic hypofractionation; the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., and used hypofractionated radiotherapy technology so that each patient received the maximum individualized radiation dose as possible

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
radiation induced esophagitis and radiation induced pneumonitis	Number of participants with treatment-related severe adverse events：Grade IV radiation esophagitis, Grade III radiation esophagitis which results in interruption of radiotherapy for 7 days or more and Grade III or above radiation pneumonitis	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTP	Record the time from the start of enrollment to the objective progression of the tumor	5 years
PFS	Record the time from the start of enrollment to the progression of disease or death	5 years
OS	Record the time from the start of enrollment to death(for any reason)	5 years
LC	Record the time from the start of enrollment to progression or primary tumors	5 years

Collaborators and Investigators

• Sponsor: The Second Hospital of Hebei Medical University
• Investigators: Study Director: Qiang Lin, Professor, North China Petroleum Bureau General Hospital, Hebei Medical University; Study Director: Chao-Xing Liu, Professor, No.1 Hospital of Shijiazhuang City; Study Director: Xiao-Ying Xue, Professor, The Second Hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 21, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: isotoxic; Non-Small-Cell Lung; hypofractionation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NSCLC isotoxic HypoRT

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